Cyclic carbonyl compounds with pendant carbonate groups, preparations thereof, and polymers therefrom

ABSTRACT

A one pot method of preparing cyclic carbonyl compounds comprising an active pendant pentafluorophenyl carbonate group is disclosed. The cyclic carbonyl compounds can be polymerized by ring opening methods to form ROP polymers comprising repeat units comprising a side chain pentafluorophenyl carbonate group. Using a suitable nucleophile, the pendant pentafluorophenyl carbonate group can be selectively transformed into a variety of other functional groups before or after the ring opening polymerization.

PARTIES TO A JOINT RESEARCH AGREEMENT

International Business Machines Corporation, a New York corporation, andCentral Glass Co., Ltd., a Tokyo, Japan corporation, are parties to aJoint Research Agreement.

BACKGROUND

The present disclosure is generally related to cyclic carbonyl compoundsfor ring-opening polymerizations and methods of preparation thereof, andmore specifically to cyclic carbonate compounds having a pendantpentafluorophenyl carbonate group. In addition, the disclosure alsorelates to the preparation of polymers having pendant pentafluorophenylcarbonate groups, which can be further reacted to form functionalizedpolymeric materials.

In general, the structural variety of cyclic carbonyl compounds for ringopening polymerization (ROP) is significantly less than the number ofcompounds available for controlled radical polymerization (CRP).However, as the effectiveness and operational simplicity oforganocatalysts improves, a wider variety of ROP compounds is sought togenerate polymer microstructures unique to ROP methods.

Initial efforts to employ substituted lactones as monomers for ROP werehampered by the sensitivity of the organocatalysts to steric bulk of thesubstituent groups, particularly those at the alpha-position. Since thealpha-position of cyclic esters is the only site capable of a generalsubstitution reaction, this approach provided limited numbers of usefulcompounds. The finding that trimethylene carbonate (TMC) was efficientlypolymerized by organocatalysts such asthiourea/1,8-diazabicyclo[5.4.0]undec-7-ene (TU/DBU) or1,5,7-triaza-bicyclo[4.4.0]dec-5-ene (TBD) was encouraging, for tworeasons: first, TMC-like compounds can be derived from readily available1,3-diols, and second, the 1,3-diols can be chosen so as to only bearsubstituents at the 2-position, which becomes the 5-position in thecyclic carbonate, where the substituent does not interfere stericallywith the ring-opening polymerization.

A number of cyclic carbonate compounds have been generated andpolymerized in the past by more conventional anionic or organometallicROP methods. Excessively bulky substituents (e.g., 2,2-diphenyl) in the1,3-diol can make ring-opening of the corresponding cyclic carbonatethermodynamically unfavorable. Thus, efforts were focused on compoundsderived from 2,2-bis(methylol)propionic acid (bisMPA), a common buildingblock for biocompatible dendrimers. For example, cyclic carbonatecompounds with a number of different functional groups attached to thecarboxylate have been generated from bisMPA (Pratt et al. Chem. Comm.2008, 114-116), Scheme 1.

wherein X is O, NH, NR′, or S, and R′ and R generally represent groupscomprising 1 to 30 carbons. The —COXR group can, for example, representan ester, amide, or thioester derived from the bisMPA carboxylic acid.

The cyclic carbonate acid compound, MTCOH,

provides great versatility in preparing functionalized carbonatecompounds for ROP, similar to (meth)acrylic acid for CRP. For example,the reaction of an alcohol or amine with (meth)acrylic acid (or(meth)acryloyl chloride) provides a (meth)acrylate or (meth)acrylamidecompound for CRP. Likewise, the reaction of an arbitrary alcohol oramine with MTCOH (or its acid chloride) can generate a cyclic carbonateester or cyclic carbonate amide compound for ROP.

However, there are only a few cyclic ester compounds bearing pendantcarbonate or carbamate groups reported in the literature. For example, acyclic carbonate bearing a chloroformate pendant group, MTCOCOCl, can besynthesized from tris(hydroxymethyl)ethane (TME) (Scheme 2).

Further substitution of the acyl chloride can afford functionalizedcarbonate compounds; however, the chloroformate intermediate suffersfrom the known limitations of acid chlorides (sensitivity to water,release of corrosive hydrogen chloride gas, difficulties in shipping andstoring). In addition, this synthetic route is labor and resourceintensive, uses significant amounts of solvent and reagents, and is notenvironmentally “green.”

Therefore, a need continues for improved methods of synthesis of cyclicester compounds containing pendant carbonate or carbamate groups.

Biodegradable polymers are of intense for use in a variety ofapplications including drug delivery/target therapeutics, imagingagents, and tissue engineering. The two most common approaches to thesynthesis of biodegradable polymers are the ring-opening polymerization(ROP) of cyclic esters (e.g., lactones) and cyclic carbonates to producepolyesters and polycarbonates, respectively, illustrated in Scheme 3.

wherein R¹ and R² generally represent hydrogen or a short chainmonovalent hydrocarbon substituent, and n is 1 to 5. As a class ofbiodegradable polymers, polycarbonates have generally been found toexhibit significantly increased rates of biodegradation in the humanbody relative to polyesters.

MTCOH-based polymers have been widely reported with a variety of sidechain groups. In these polymers, the side chain groups may beincorporated prior to polymerization via the synthesis of afunctionalized monomer. Alternatively, cyclic carbonate monomers basedon a protected variant of MTC-OH (most commonly the benzyl ester shown)can be polymerized and desired substituent groups later added to thepolymer via post-polymerization modification (as shown in Scheme 4).This post-polymerization modification process typically encompassesremoving the protecting group followed by coupling a new substituentgroup to the carboxylic acid group via the formation of an esterlinkage, an amide linkage, or the like.

However, as a result of the limitations of the known art, few polymersbearing substituent groups attached by side-chain carbonate, carbamate,or other such linkages are known. A more versatile and straightforwardapproach to the preparation of ROP polymers bearing functionalized sidechain groups is needed, in particular polycarbonates bearing reactivecarbonate side chain groups. The reactive side chain groups shouldenable direct functionalization of the ROP polymer.

SUMMARY

Accordingly, disclosed is a composition, comprising:

a first cyclic carbonyl compound of the general formula (2):

wherein

each Y is a divalent radical independently selected from the groupconsisting of —O—, —S—, —N(H)—, or —N(Q″)-, wherein each Q″ group is amonovalent radical independently selected from the group consisting ofalkyl groups comprising 1 to 30 carbons, aryl groups comprising 6 to 30carbons, and the foregoing Q″ groups substituted with apentafluorophenyl carbonate group,

n′ is 0 or an integer from 1 to 10, wherein when n′ is 0, carbonslabeled 4 and 6 are linked together by a single bond,

each Q′ group is a monovalent radical independently selected from thegroup consisting of hydrogen, halides, pentafluorophenyl carbonategroup, alkyl groups comprising 1 to 30 carbons, alkene groups comprising1 to 30 carbons, alkyne groups comprising 1 to 30 carbons, aryl groupscomprising 6 to 30 carbons, ester groups comprising 1 to 30 carbons,amide groups comprising 1 to 30 carbons, thioester groups comprising 1to 30 carbons, urea groups comprising 1 to 30 carbons, carbamate groupscomprising 1 to 30 carbons, ether groups comprising 1 to 30 carbons,alkoxy groups comprising 1 to 30 carbons, and the foregoing Q′ groupssubstituted with a pentafluorophenyl carbonate group, and wherein

one or more of the Q′ and/or Q″ groups comprises a pentafluorophenylcarbonate group.

Also disclosed is composition, comprising:

a first cyclic carbonate compound of the general formula (5):

wherein

m and n are each independently 0 or an integer from 1 to 11, wherein mand n cannot together be 0, and m+n is less than or equal to 11,

R¹ is a monovalent radical selected from the group consisting ofhydrogen, halides, and alkyl groups comprising 1 to 30 carbons,

each V′ group is monovalent radical independently selected from thegroup consisting of hydrogen, halides, pentafluorophenyl carbonate group(—OCO₂C₆F₅), alkyl groups comprising 1 to 30 carbons, alkene groupscomprising 1 to 30 carbons, alkyne groups comprising 1 to 30 carbons,aryl groups comprising 6 to 30 carbons, ester groups comprising 1 to 30carbons, amide groups comprising 1 to 30 carbons, thioester groupscomprising 1 to 30 carbons, urea groups comprising 1 to 30 carbons,carbamate groups comprising 1 to 30 carbons, ether groups comprising 1to 30 carbons, alkoxy groups comprising 1 to 30 carbons, and theforegoing V′ groups substituted with a pentafluorophenyl carbonategroup, and

L′ is a single bond or a divalent linking group selected from the groupconsisting of alkyl groups comprising 1 to 30 carbons, alkene groupscomprising 1 to 30 carbons, alkyne groups comprising 1 to 30 carbons,aryl groups comprising 6 to 30 carbons, ester groups comprising 1 to 30carbons, amide groups comprising 1 to 30 carbons, thioester groupscomprising 1 to 30 carbons, urea groups comprising 1 to 30 carbons,carbamate groups comprising 1 to 30 carbons, and ether groups comprising1 to 30 carbons.

A method is disclosed, comprising:

forming a first mixture comprising bis(pentafluorophenyl) carbonate, acatalyst, an optional solvent, and a precursor compound, the precursorcompound comprising i) three or more carbons, ii) a first hydroxy groupcapable of forming a pentafluorophenyl carbonate in a reaction withbis(pentafluorophenyl) carbonate, and iii) two nucleophilic groupsindependently selected from the group consisting of alcohols, amines,and thiols, the two nucleophilic groups capable of forming a cycliccarbonyl group in a reaction with bis(pentafluorophenyl) carbonate;

agitating the first mixture, thereby forming a first cyclic carbonylcompound comprising i) a pendant pentafluorophenyl carbonate group andii) a cyclic carbonyl moiety selected from the group consisting ofcyclic carbonates, cyclic ureas, cyclic carbamates, cyclicthiocarbamates, cyclic thiocarbonates, and cyclic dithiocarbonates.

Another method comprises:

agitating a first mixture comprising i) a precursor compound comprisingtwo or more carbons and three or more hydroxy groups, ii)bis(pentafluorophenyl) carbonate, and iii) a catalyst, thereby forming afirst cyclic carbonate compound comprising a pendant pentafluorophenylcarbonate group.

Yet another method comprises:

forming a mixture comprising i) a first cyclic carbonyl compoundcomprising a cyclic carbonyl moiety selected from the group consistingof cyclic carbonates, cyclic ureas, cyclic carbamates, cyclicthiocarbamates, cyclic thiocarbonates, and cyclic dithiocarbonates, anda pendant pentafluorophenyl carbonate group, ii) a nucleophile selectedfrom the group consisting of alcohols, amines, and thiols, iii) anoptional catalyst, and iv) an optional solvent;

agitating the mixture, thereby forming a second cyclic carbonyl compoundand pentafluorophenol byproduct, wherein the second cyclic carbonylcompound comprises a second functional group formed by a reaction of thependant pentafluorophenyl carbonate group with the nucleophile, thesecond functional group selected from the group consisting of carbonatesother than pentafluorophenyl carbonate, carbamates, and thiocarbonates.

Still another method comprises:

agitating a first mixture comprising a catalyst, an initiator, anoptional accelerator, an optional solvent, and a first cyclic carbonylcompound comprising a pentafluorophenyl carbonate group, thereby forminga ROP polymer by ring opening polymerization of the first cycliccarbonyl compound, the ROP polymer comprising a chain fragment derivedfrom the initiator, and a first polymer chain; wherein i) the chainfragment comprises a first backbone heteroatom, the first backboneheteroatom linked to a first end unit of the first polymer chain, thefirst backbone heteroatom selected from the group consisting of oxygen,nitrogen, and sulfur, ii) the first polymer chain comprises a second endunit comprising a nucleophilic group selected from the group consistingof hydroxy group, primary amine groups, secondary amine groups, andthiol group, and iii) the first polymer chain comprises a first repeatunit, the first repeat unit comprising a) a backbone functional groupselected from the group consisting of carbonate, ureas, carbamates,thiocarbamates, thiocarbonate, and dithiocarbonate, and b) a tetrahedralbackbone carbon, the tetrahedral backbone carbon being linked to a firstside chain comprising a pentafluorophenyl carbonate group.

Further disclosed is a biodegradable polymer, comprising:

a chain fragment; and

a first polymer chain; wherein i) the chain fragment comprises a firstbackbone heteroatom, the first backbone heteroatom linked to a first endunit of the first polymer chain, the first backbone heteroatom selectedfrom the group consisting of oxygen, nitrogen, and sulfur, ii) the firstpolymer chain comprises a second end unit comprising a nucleophilicgroup selected from the group consisting of hydroxy group, primary aminegroups, secondary amine groups, and thiol group, and iii) the firstpolymer chain comprises a first repeat unit, the first repeat unitcomprising a) a backbone functional group selected from the groupconsisting of carbonate, ureas, carbamates, thiocarbamates,thiocarbonate, and dithiocarbonate, and b) a tetrahedral backbonecarbon, the tetrahedral backbone carbon being linked to a first sidechain comprising a pentafluorophenyl carbonate group.

The above-described and other features and advantages of the presentinvention will be appreciated and understood by those skilled in the artfrom the following detailed description, drawings, and appended claims.

DETAILED DESCRIPTION

Cyclic carbonyl compounds are disclosed comprising a pendantpentafluorophenyl carbonate group and a functional group selected fromcyclic carbonate, cyclic carbamate, cyclic urea, cyclic thiocarbonate,cyclic thiocarbamate, cyclic dithiocarbonate, and combinations thereof.Also described is a simple one step method (Method 1) for preparing acyclic carbonyl compound having a pendant pentafluorophenyl carbonategroup, referred to herein as the first cyclic carbonyl compound. Furtherdisclosed is a method (Method 2) of preparing a second cyclic carbonylcompound, by reacting the pendant pentafluorophenyl carbonate group ofthe first cyclic carbonyl compound with an alcohol, amine or thiol toform a different carbonate, a carbamate or a thiocarbonate respectively,without altering the cyclic carbonyl moiety of the first cyclic carbonylcompound. Each of the described methods is mild, high yielding, andenvironmentally safer than methods involving reagents such as phosgene,or intermediate acid chlorides. The first and second cyclic carbonylcompounds are potentially capable of forming biodegradable polymers byring opening polymerization (ROP), in particular polycarbonates havingunique pendant functionalities and properties.

The term “biodegradable” is defined by the American Society for Testingand Materials as a degradation caused by biological activity, especiallyby enzymatic action, leading to a significant change in the chemicalstructure of the material. For purposes herein, a material isbiodegradable if it undergoes 60% biodegradation within 180 days inaccordance with ASTM D6400.

The first cyclic carbonyl compound bearing a pendant pentafluorophenylcarbonate group is prepared by the reaction of bis(pentafluorophenyl)carbonate:

with a precursor compound. The precursor compound comprises three ormore carbons and three or more nucleophilic groups selected from thegroup consisting of alcohols, thiols, and amines. One of the three ormore nucleophilic groups is a hydroxy group that reacts with PFC to forma pendant pentafluorophenyl carbonate group. This hydroxy group isreferred to herein as a “pentafluorophenyl carbonate forming hydroxygroup.” Two of the three or more nucleophilic groups of the precursorcompound react with PFC to form a cyclic carbonyl group, and arereferred to as “cyclic carbonyl forming nucleophilic groups.”

The precursor compounds have the general formula (1):

wherein

together the X groups are cyclic carbonyl forming nucleophilic groups,

each X independently represents a monovalent radical selected from thegroup consisting of —OH, —SH, —NH₂, and —NHR″, wherein each R″ groupindependently represents a monovalent radical selected from the groupconsisting of alkyl groups comprising 1 to 30 carbons, aryl groupscomprising 6 to 30 carbons, and the foregoing R″ groups substituted witha pentafluorophenyl carbonate forming hydroxy group,

n′ is 0 or an integer from 1 to 10, wherein when n′ is 0 carbons labeled1 and 3 attached to each X group are linked together by a single bond,

each R′ group independently represents a monovalent radical selectedfrom the group consisting of hydrogen, pentafluorophenyl carbonateforming hydroxy group, halides, alkyl groups comprising 1 to 30 carbons,alkene groups comprising 1 to 30 carbons, alkyne groups comprising 1 to30 carbons, aryl groups comprising 6 to 30 carbons, ester groupscomprising 1 to 30 carbons, amide groups comprising 1 to 30 carbons,thioester groups comprising 1 to 30 carbons, urea groups comprising 1 to30 carbons, carbamate groups comprising 1 to 30 carbons, ether groupscomprising 1 to 30 carbons, alkoxy groups comprising 1 to 30 carbons,and the foregoing R′ groups substituted with a pentafluorophenylcarbonate forming hydroxy group, and

at least one of the foregoing R′ and/or R″ groups comprises apentafluorophenyl carbonate forming hydroxy group.

The R′ and R″ groups can further independently comprise a cycloaliphaticring, an aromatic ring, and/or a heteroatom such as oxygen, sulfur ornitrogen. In an embodiment, the X groups of the precursor compound arehydroxy groups capable of forming a cyclic carbonate in a reaction withPFC.

Non-limiting examples of cyclic carbonyl forming moieties include1,2-ethanediol groups, 1,3-propanediol groups, 1,4-butanediol groups,1,2-ethanediamine groups, 1,3-propanediamine groups, 1,4-butanediaminegroups, 2-aminoethanol groups, 3-amino-1-propanol groups,4-amino-1-butanol groups, 2-mercaptoethanol groups,3-mercapto-1-propanol groups, 1-mercapto-2-propanol groups,4-mercapto-1-butanol groups, cysteamine groups, 1,2-ethanedithiolgroups, and 1,3-propanedithiol groups. Cyclic carbonyl groups formed bythe foregoing moieties in a reaction with PFC include cyclic carbonatesfrom any of the above diols, cyclic ureas from any of the abovediamines, cyclic carbamates from any of the above amino-alcohols, cyclicthiocarbonates from any of the above mercapto-alcohols, cyclicthiocarbamates from any of the above amino-thiols, and cyclicdithiocarbonates from any of the above dithiols. These functional groupsare listed in Table 1.

TABLE 1 Cyclic Carbonate

Cyclic Urea

Cyclic Carbamate

Cyclic Thiocarbamate

Cyclic Thiocarbonate

Cyclic Dithiocarbonate

The first cyclic carbonyl compound comprises a cyclic carbonyl moietyselected from the group consisting of cyclic carbonates, cycliccarbamates, cyclic ureas, cyclic thiocarbonates, cyclic thiocarbamates,cyclic dithiocarbonates, and combinations thereof, formed by reaction ofthe two X groups with PFC. The first cyclic carbonyl compound furthercomprises a pendant pentafluorophenyl carbonate group (i.e., the moiety—OCO₂C₆F₅) derived from a pentafluorophenyl carbonate forming hydroxygroup of an R′ and/or R″ group.

The first cyclic carbonyl compounds are represented by the generalformula (2):

wherein

each Y is a divalent radical independently selected from the groupconsisting of —O—, —S—, —N(H)—, or —N(Q″)-, wherein each Q″ group is amonovalent radical independently selected from the group consisting ofalkyl groups comprising 1 to 30 carbons, aryl groups comprising 6 to 30carbons, and the foregoing Q″ groups substituted with apentafluorophenyl carbonate group (i.e., —OCO₂C₆F₅),

n′ is 0 or an integer from 1 to 10, wherein when n′ is 0, carbonslabeled 4 and 6 are linked together by a single bond,

each Q′ group is a monovalent radical independently selected from thegroup consisting of hydrogen, halides, a pentafluorophenyl carbonategroup, alkyl groups comprising 1 to 30 carbons, alkene groups comprising1 to 30 carbons, alkyne groups comprising 1 to 30 carbons, aryl groupscomprising 6 to 30 carbons, ester groups comprising 1 to 30 carbons,amide groups comprising 1 to 30 carbons, thioester groups comprising 1to 30 carbons, urea groups comprising 1 to 30 carbons, carbamate groupscomprising 1 to 30 carbons, ether groups comprising 1 to 30 carbons,alkoxy groups comprising 1 to 30 carbons, and the foregoing Q′ groupssubstituted with a pentafluorophenyl carbonate group, and wherein

one or more of the Q′ and/or Q″ groups comprises a pentafluorophenylcarbonate group.

The Y groups in formula (2) are derived from the X groups of formula(1). In an embodiment, each Y in formula (2) is —O— and the first cycliccarbonyl compound comprises a cyclic carbonate group. In anotherembodiment, the first cyclic carbonyl compound comprises a singlependant pentafluorophenyl carbonate group.

The cyclic carbonyl group and the pendant pentafluorophenyl carbonatemoiety are formed in one step from the precursor compound using PFC anda suitable catalyst. PFC is less toxic than other reagents (e.g.,phosgene) in preparing cyclic carbonate compounds. PFC is a crystallinesolid at room temperature that, being less sensitive to water thanphosgene, can be easily stored, shipped, and handled. PFC does notrequire elaborate reaction and workup conditions. Moreover, thepentafluorophenol byproduct of the cyclization reaction is lessvolatile, less acidic, and less corrosive than hydrochloric acid. Theseadvantages reduce the cost and complexity of the reactions, andpotentially widen the scope of the starting materials to includecompounds containing acid-sensitive groups. In addition, thepentafluorophenol byproduct of the cyclization reaction can be readilyrecycled back into PFC.

Isomerically pure precursor compounds having a hydrogen attached to anasymmetric carbon can be converted to a cyclic carbonyl compoundcomprising a pentafluorophenyl carbonate group without undergoingsignificant racemization. The esterification conditions are effective inachieving an enantiomeric excess of 80% or more, more specifically of90%. In an embodiment, the cyclic carbonyl compound comprises anasymmetric carbon as an (R) isomer, in an enantiomeric excess of greaterthan 80%, more specifically greater than 90%. In another embodiment, thecyclic carbonyl compound comprises an asymmetric carbon as an (S)isomer, in an enantiomeric excess greater than 80%, more specificallygreater than 90%.

More specific precursor compounds are represented by the general formula(3):

wherein

the X′ groups together are cyclic carbonyl forming nucleophilic groups,

m and n are each independently 0 or an integer from 1 to 11, wherein mand n cannot together be 0, and m+n is an integer less than or equal to11,

each X′ is a monovalent radical independently selected from the groupconsisting of —OH, —SH, —NH₂, and —NHT″, wherein each T″ is a monovalentradical independently selected from the group consisting of alkyl groupscomprising 1 to 30 carbons, aryl groups comprising 6 to 30 carbons, andthe foregoing T″ groups substituted with a pentafluorophenyl carbonateforming hydroxy group,

each T′ is a monovalent radical independently selected from the groupconsisting of hydrogen, halides, pentafluorophenyl carbonate forminghydroxy group, alkyl groups comprising 1 to 30 carbons, alkene groupscomprising 1 to 30 carbons, alkyne groups comprising 1 to 30 carbons,aryl groups comprising 6 to 30 carbons, ester groups comprising 1 to 30carbons, amide groups comprising 1 to 30 carbons, thioester groupscomprising 1 to 30 carbons, urea groups comprising 1 to 30 carbons,carbamate groups comprising 1 to 30 carbons, ether groups comprising 1to 30 carbons, alkoxy groups comprising 1 to 30 carbons, and theforegoing T′ groups substituted with a pentafluorophenyl carbonateforming hydroxy group, and

L′ is a single bond or a divalent linking group selected from the groupconsisting of alkyl groups comprising 1 to 30 carbons, alkene groupscomprising 1 to 30 carbons, alkyne groups comprising 1 to 30 carbons,aryl groups comprising 6 to 30 carbons, ester groups comprising 1 to 30carbons, amide groups comprising 1 to 30 carbons, thioester groupscomprising 1 to 30 carbons, urea groups comprising 1 to 30 carbons,carbamate groups comprising 1 to 30 carbons, and ether groups comprising1 to 30 carbons.

The T′ and T″ groups can further independently comprise a cycloaliphaticring, an aromatic ring, and/or a heteroatom such as oxygen, sulfur ornitrogen. In an embodiment, none of the T′ or T″ groups comprises apentafluorophenyl carbonate forming hydroxy group. In anotherembodiment, the T′ group attached to carbon labeled 2 in formula (3) isethyl or methyl, and all other T′ groups are hydrogen. In anotherembodiment, the T′ group attached to carbon labeled 2 in formula (3) isethyl or methyl, carbon labeled 2 in formula (3) is an asymmetriccenter, and the precursor compound comprises the (R) or (S) isomer ingreater than 80% enantiomeric excess.

The corresponding first cyclic carbonyl compounds formed by theprecursor compounds of formula (3) have the general formula (4):

wherein

m and n are each independently 0 or an integer from 1 to 11, wherein mand n cannot together be 0, and m+n is an integer less than or equal to11,

each Y′ is a divalent radical independently selected from the groupconsisting of —O—, —S—, —N(H)— and —N(V″)-, wherein each V″ group is amonovalent radical independently selected from the group consisting ofalkyl groups comprising 1 to 30 carbons, aryl groups comprising 1 to 30carbons, and a foregoing V″ group substituted with a pentafluorophenylcarbonate group (—OCO₂C₆F₅),

each V′ group is a monovalent radical independently selected from thegroup consisting of hydrogen, halides, pentafluorophenyl carbonategroup, alkyl groups comprising 1 to 30 carbons, alkene groups comprising1 to 30 carbons, alkyne groups comprising 1 to 30 carbons, aryl groupscomprising 6 to 30 carbons, ester groups comprising 1 to 30 carbons,amide groups comprising 1 to 30 carbons, thioester groups comprising 1to 30 carbons, urea groups comprising 1 to 30 carbons, carbamate groupscomprising 1 to 30 carbons, ether groups comprising 1 to 30 carbons,alkoxy groups comprising 1 to 30 carbons, and a foregoing V′ groupsubstituted with a pentafluorophenyl carbonate group, and

L′ is a single bond or a divalent linking group selected from the groupconsisting of alkyl groups comprising 1 to 30 carbons, alkene groupscomprising 1 to 30 carbons, alkyne groups comprising 1 to 30 carbons,aryl groups comprising 6 to 30 carbons, ester groups comprising 1 to 30carbons, amide groups comprising 1 to 30 carbons, thioester groupscomprising 1 to 30 carbons, urea groups comprising 1 to 30 carbons,carbamate groups comprising 1 to 30 carbons, and ether groups comprising1 to 30 carbons.

In an embodiment, no V′ group and no V″ group comprises apentafluorophenyl carbonate group. In another embodiment, the V′ groupattached to the carbon labeled 5 in formula (4) is ethyl or methyl, andall other V′ groups are hydrogen. In an embodiment, the V′ groupattached to carbon labeled 5 in formula (4) is ethyl or methyl, carbonlabeled 5 in formula (4) is an asymmetric center, and the cycliccarbonyl compound comprises the (R) or (S) isomer in greater than 80%enantiomeric excess. In another embodiment, each Y′ is —O—, and V′ atposition labeled 5 in formula (4) is a monovalent radical selected fromthe group consisting of hydrogen, halides, and alkyl groups comprising 1to 30 carbons.

Even more specific first cyclic carbonyl compounds are cyclic carbonateshaving the general formula (5):

wherein

m and n are each independently 0 or an integer from 1 to 11, wherein mand n cannot together be 0, and m+n is less than or equal to 11,

R¹ is a monovalent radical selected from the group consisting ofhydrogen, halides, and alkyl groups comprising 1 to 30 carbons,

each V′ group is monovalent radical independently selected from thegroup consisting of hydrogen, halides, pentafluorophenyl carbonate group(—OCO₂C₆F₅), alkyl groups comprising 1 to 30 carbons, alkene groupscomprising 1 to 30 carbons, alkyne groups comprising 1 to 30 carbons,aryl groups comprising 6 to 30 carbons, ester groups comprising 1 to 30carbons, amide groups comprising 1 to 30 carbons, thioester groupscomprising 1 to 30 carbons, urea groups comprising 1 to 30 carbons,carbamate groups comprising 1 to 30 carbons, ether groups comprising 1to 30 carbons, alkoxy groups comprising 1 to 30 carbons, and theforegoing V′ groups substituted with a pentafluorophenyl carbonategroup, and

L′ is a single bond or a divalent linking group selected from the groupconsisting of alkyl groups comprising 1 to 30 carbons, alkene groupscomprising 1 to 30 carbons, alkyne groups comprising 1 to 30 carbons,aryl groups comprising 6 to 30 carbons, ester groups comprising 1 to 30carbons, amide groups comprising 1 to 30 carbons, thioester groupscomprising 1 to 30 carbons, urea groups comprising 1 to 30 carbons,carbamate groups comprising 1 to 30 carbons, and ether groups comprising1 to 30 carbons.

R¹ and L′ can together form a first ring comprising 3 to 10 carbons.Each V′ can independently form a second ring with a different V′ group,with R¹, with L′, or combinations thereof, wherein the second ringcomprises 3 to 10 carbons.

In an embodiment, the cyclic carbonate compound of formula (5) comprisesa single pentafluorophenyl carbonate group. In another embodiment, eachV′ is hydrogen. In another embodiment, m and n are equal to 1, and R¹ isa monovalent hydrocarbon group comprising 1 to 10 carbons. In anotherembodiment, R¹ is selected from the group consisting of methyl, ethyl,propyl, 2-propyl, n-butyl, 2-butyl, sec-butyl (2-methylpropyl), t-butyl(1,1-dimethylethyl), n-pentyl, 2-pentyl, 3-pentyl, iso-pentyl, andneo-pentyl.

Even more specific first cyclic carbonate monomers are represented bythe general formula (6):

wherein

m and n are each independently 0 or an integer from 1 to 11, wherein mand n cannot together be 0, and m+n is less than or equal to 11,

R¹ is a monovalent radical selected from the group consisting ofhydrogen, halides, and alkyl groups comprising 1 to 30 carbons, and

L′ is a single bond or a divalent linking group selected from the groupconsisting of alkyl groups comprising 1 to 30 carbons, alkene groupscomprising 1 to 30 carbons, alkyne groups comprising 1 to 30 carbons,aryl groups comprising 6 to 30 carbons, ester groups comprising 1 to 30carbons, amide groups comprising 1 to 30 carbons, thioester groupscomprising 1 to 30 carbons, urea groups comprising 1 to 30 carbons,carbamate groups comprising 1 to 30 carbons, and ether groups comprising1 to 30 carbons.

R¹ and L′ can together form a first ring comprising 3 to 10 carbons.Each V′ can independently form a second ring with a different V′ group,with R¹, with L′, or combinations thereof, wherein the second ringcomprises 3 to 10 carbons.

In an embodiment, m and n are each independently 0 or an integer from 1to 3, wherein m and n together cannot be 0. In another embodiment, m andn are each equal to 1, and R¹ is a monovalent hydrocarbon groupcomprising 1 to 10 carbons. Exemplary R¹ groups include, for example,methyl, ethyl, propyl, 2-propyl, n-butyl, 2-butyl, sec-butyl(2-methylpropyl), t-butyl (1,1-dimethylethyl), n-pentyl, 2-pentyl,3-pentyl, iso-pentyl, and neo-pentyl.

In an embodiment, the first cyclic carbonate compound is selected fromthe group consisting of

Method 1. Preparation of the First Cyclic Carbonyl Compound

A method (Method 1) of preparing a first cyclic carbonyl compoundbearing a pendant pentafluorophenyl carbonate group comprises forming afirst mixture comprising bis(pentafluorophenyl) carbonate, a catalyst,an optional solvent, and a precursor compound, the precursor compoundcomprising i) three or more carbons, ii) a first hydroxy group capableof forming a pentafluorophenyl carbonate in a reaction withbis(pentafluorophenyl) carbonate, and iii) two nucleophilic groups(e.g., the X groups in formula (1) or the X′ groups in formula (3))independently selected from the group consisting of alcohols, amines,and thiols, the two nucleophilic groups capable of forming a cycliccarbonyl group in a reaction with bis(pentafluorophenyl) carbonate. Thefirst mixture is agitated at a temperature effective in forming a firstcyclic carbonyl compound. The first cyclic carbonyl compound comprisesi) a pendant pentafluorophenyl carbonate group and ii) a cyclic carbonylmoiety selected from the group consisting of cyclic carbonates, cyclicureas, cyclic carbamates, cyclic thiocarbamates, cyclic thiocarbonates,and cyclic dithiocarbonates.

The formation of the cyclic carbonyl moiety and the pendantpentafluorophenyl carbonate can occur in a single process step undermild conditions.

The precursor compound can comprise more than one pentafluorophenylcarbonate forming hydroxy group and more than two nucleophilic groupscapable of forming a cyclic carbonyl group in a reaction withbis(pentafluorophenyl) carbonate. Consequently, the first cycliccarbonyl monomer can comprise more than one cyclic carbonyl moiety andmore than one pendant pentafluorophenyl carbonate group. In anembodiment, the first cyclic carbonyl compound comprises onepentafluorophenyl carbonate group. In another embodiment, the firstcyclic carbonyl compound comprises one cyclic carbonyl moiety.

In a specific embodiment, a method comprises agitating a first mixturecomprising i) a precursor compound comprising three or more carbons andthree or more hydroxy groups, ii) bis(pentafluorophenyl) carbonate, andiii) a catalyst, thereby forming a first cyclic carbonate compoundcomprising a pendant pentafluorophenyl carbonate group.

As a non-limiting example, the preparation of cyclic carbonate compoundTMCPFP is illustrated in Scheme 5. TMCPFP is formed by the reaction ofthe biocompatible precursor compound, tris(hydroxymethyl)ethane (TME),also known as 1,1,1-trimethylolethane, with PFC.

Carbon 5 of the ring is attached to a pendant methylenepentafluorophenyl carbonate group (i.e., —CH₂OCO₂C₆F₅) and a pendantmethyl group. The reaction can be conducted using about 2 to about 2.5molar equivalents of PFC, more specifically 2.2 to 2.3 molarequivalents, for each mole of tris(hydroxymethyl)ethane. Generally, 3moles of pentafluorophenol are produced as a byproduct (not shown) per 2moles of PFC used. Each theoretical mole of pentafluorophenol byproductcan be recovered in 90% to 100% yield for recycling back to PFC. In anembodiment, the theoretical amount of pentafluorophenol byproduct isquantitatively recovered for recycling back to PFC. TMCPFP is a white,crystalline powder which can be easily handled, manipulated, stored, andshipped.

The use of PFC eliminates the multi-step process usingprotection/deprotection reactions, eliminates the use of expensiveand/or hazardous reagents, and eliminates the multiple wasteful work-upsin the prior art synthetic pathway to cyclic carbonate compounds. Byreducing waste, eliminating hazardous reagents, and using recyclablematerials, the process improves the overall environmental compatibilityof the process of preparing functionalized cyclic carbonate compounds.

Exemplary precursor compounds for preparing cyclic carbonates bearing apendant pentafluorophenyl carbonate group include but are not limited totriols such as 1,1,1-trimethylol ethane (TME), 1,1,1-trimethylolpropane, 1,2,3-propane triol, 2-hydroxymethyl-1,3-propanediol,2-(hydroxymethyl)-2-methyl-1,3-propane diol, butane-1,2,3-triol,butane-1,2,4-triol, 1,1,1-trimethylol butane; 1,1,1-trimethylol pentane;1,2,5-pentane triol, 1,1,1-trimethylol hexane, 1,2,3-hexane triol,1,2,6-hexane triol, cyclohexane-1,2,3-triol, cyclohexane-1,2,4-triol,cyclohexane-1,3,5-triol, 2,5-dimethyl-1,2,6-hexanetriol,1,1,1-trimethylol heptane, 1,2,3-heptanetriol,4,5-dideoxy-d-erythro-pent-4-enitol,3,5,5-trimethyl-2,2-dihydroxymethylhexane-1-ol. Exemplary precursorcompounds comprising more than three hydroxy groups include erythritol,pentaerythritol, dipentaerythritol, ditrimethylol propane, diglycerol,and ditrimethylol ethane.

Another challenge in preparing cyclic carbonyl monomers, for examplecyclic carbonates from 1,3-diols, is achieving selective ring closurewithout polymerization, which depends on the nucleophilicity of theleaving group and the catalyst used. Advantageously, thepentafluorophenol byproduct is a weak nucleophile and does not initiatepolymerization. In an embodiment, the cyclic carbonyl forming reactionwith PFC produces more than 0 to less than 2.0 wt. % of a polymerbyproduct derived from the precursor compound, based on the weight ofthe precursor compound. In another embodiment, the cyclic carbonylforming reaction with PFC produces no detectable polymer byproduct.

The first mixture comprises a catalyst suitably chosen to activate thenucleophilic hydroxy functional groups and not the electrophilic PFCcarbonyl group. Exemplary catalysts include tertiary amines, for example1,8-bis(dimethylamino)naphthalene, referred to also as PROTON SPONGE, atrademark of Sigma-Aldrich. Still other catalysts include halide saltsof Group I elements, particularly lithium (Li), sodium (Na), potassium(K), rubidium (Rb), cesium (Cs), or francium (Fr). In one embodiment thecatalyst is CsF.

The catalyst can be present in an amount of 0.02 to 1.00 moles per moleof the precursor compound, more particularly 0.05 to 0.50 moles per moleof the precursor compound, and even more particularly 0.15 to 0.25 molesper mole of the precursor compound.

The first mixture optionally includes a solvent such as tetrahydrofuran,acetonitrile (many other solvents can be used as well), or combinationsthereof. When a solvent is present, the concentration of precursorcompound in the solvent can be from about 0.01 to about 10 moles perliter, more typically about 0.02 to 0.8 moles per liter, morespecifically 0.1 to 0.6 moles per liter, or most specifically 0.15 to0.25 moles per liter. In one embodiment, the reaction mixture consistsof the precursor compound, PFC, a catalyst and a solvent. In oneembodiment the solvent is anhydrous.

The first mixture is agitated at a temperature suitable for convertingthe precursor compound into a first cyclic carbonyl compound. Thetemperature can be from −20° C. to 100° C., 0° C. to 80° C., 10° C. to50° C., or more specifically ambient or room temperature, typically 17°C. to 30° C. Optionally, the reaction mixture is agitated under an inertatmosphere. In one embodiment, the temperature is ambient temperature.Care should be taken to avoid an initial mild exotherm during reagentmixing which may lead to the formation of unwanted dimeric carbonateby-products.

Agitation of the first mixture can be conducted for a period of 1 hourto 120 hours, 5 hours to 48 hours, and more specifically 12 hours to 36hours. In one embodiment, agitation is conducted for 15 to 24 hours atambient temperature.

The second mixture comprises the first cyclic carbonyl compoundcomprising the pendant pentafluorophenyl carbonate group andpentafluorophenol byproduct. The first cyclic carbonyl monomer can beisolated using any known method of purification, including distillation,chromatography, extraction, precipitation, and recrystallization. In oneembodiment, the first cyclic carbonyl compound is purified by selectiveprecipitation of the pentafluorophenol byproduct or the first cycliccarbonyl monomer from the second mixture. In one variation on selectiveprecipitation, the reaction mixture comprises a first solvent in whichthe precursor compound, PFC, first cyclic carbonyl monomer andpentafluorophenol byproduct are highly soluble. Upon completion of thereaction to form the first cyclic carbonyl compound, the first solventis removed by, for example, vacuum distillation, followed by addition ofa second solvent suitably chosen to selectively precipitate thepentafluorophenol byproduct or the first cyclic carbonyl compound. Inanother variation, the first solvent can be selected to facilitateprecipitation of the first cyclic carbonyl compound or thepentafluorophenol byproduct from the second mixture as the reactionproceeds. In yet another variation, after removal of thepentafluorophenol byproduct, the first cyclic carbonyl compound isfurther purified by recrystallization.

The method (Method 1) can further comprise the step of recovering thepentafluorophenol byproduct for recycling. The yield of recoveredpentafluorophenol byproduct from the second mixture is about 80% to100%, more specifically 90% to 100%, based on the theoretical amount ofpentafluorophenol byproduct formed. More particularly, thepentafluorophenol byproduct can be quantitatively recovered forrecycling back to PFC.

Method 2. Functionalization of the First Cyclic Carbonyl Compound

Also disclosed is a mild method (Method 2) of preparing a second cycliccarbonyl compound from the first cyclic carbonyl compound by selectivelyreacting the first cyclic carbonyl compound with a nucleophile such asan alcohol, amine, or thiol, without altering the cyclic carbonyl moietyof the first cyclic carbonyl compound, thereby forming a second cycliccarbonyl compound and pentafluorophenol byproduct. In this reaction, thependant pentafluorophenyl carbonate group is converted to a secondfunctional group selected from the group consisting of carbonates otherthan pentafluorophenyl carbonate, carbamates, and thiocarbonates. Thesecond functional group can comprise from 1 to 10000 carbons. Anoptional catalyst can be used with weaker nucleophiles such as alcoholswhen forming the second cyclic carbonyl compound. Generally, a catalystis not required for the reaction of a pendant pentafluorophenylcarbonate group with stronger nucleophiles (e.g., primary amines). In anembodiment, the second cyclic carbonyl compound comprises nopentafluorophenyl carbonate groups.

The second cyclic carbonyl compounds can have the general formula (7):

wherein

n′ is 0 or an integer from 1 to 10, wherein when n′ is 0 carbons labeled4 and 6 are linked together by a single bond,

each W′ is a divalent radical independently selected from the groupconsisting of —O—, —S—, —N(H)— or —N(W″), wherein each W″ groupindependently represents a monovalent radical selected from the groupconsisting of alkyl groups comprising 1 to 30 carbons, aryl groupscomprising 1 to 30 carbons, and the foregoing W″ groups substituted witha second functional group selected from the group consisting ofcarbonates other than pentafluorophenyl carbonate, carbamates, andthiocarbonates,

each Z′ group independently represents monovalent radical selected fromthe group consisting of hydrogen, a second functional group selectedfrom the group consisting of carbonates other than pentafluorophenylcarbonate, carbamates, and thiocarbonates, halides, alkyl groupscomprising 1 to 30 carbons, alkene groups comprising 1 to 30 carbons,alkyne groups comprising 1 to 30 carbons, aryl groups comprising 6 to 30carbons, ester groups comprising 1 to 30 carbons, amide groupscomprising 1 to 30 carbons, aryl groups comprising 6 to 30 carbons,thioester groups comprising 1 to 30 carbons, urea groups comprising 1 to30 carbons, carbamate groups comprising 1 to 30 carbons, ether groupscomprising 1 to 30 carbons, alkoxy groups comprising 1 to 30 carbons,and the foregoing Z′ groups substituted with a second functional groupselected from the group consisting of a carbonates other thanpentafluorophenyl carbonate, carbamates, and thiocarbonates.

In an embodiment, the second cyclic carbonyl compound comprises nopentafluorophenyl ester group (i.e., —CO₂PFP), and no pentafluorophenylcarbonate group (i.e., —OCO₂PFP).

A more specific second cyclic carbonyl compound has the general formula(8):

wherein

m and n are each independently 0 or an integer from 1 to 11, wherein mand n cannot together be 0, and m+n equals an integer from 1 to 11,

each W′ independently represents divalent radical selected from thegroup consisting of O, S, NH or NW″, wherein each W″ group independentlyrepresents a monovalent radical selected from the group consisting ofalkyl groups comprising 1 to 30 carbons, and aryl groups comprising 1 to30 carbons, and the foregoing W″ groups substituted with a secondfunctional group selected from the group consisting of a carbonatesother than pentafluorophenyl carbonate, carbamates, and thiocarbonates,

L′ represents a single bond or a divalent linking group selected fromthe group consisting of alkyl groups comprising 1 to 30 carbons, alkenegroups comprising 1 to 30 carbons, alkyne groups comprising 1 to 30carbons, aryl groups comprising 6 to 30 carbons, ester groups comprising1 to 30 carbons, amide groups comprising 1 to 30 carbons, thioestergroups comprising 1 to 30 carbons, urea groups comprising 1 to 30carbons, carbamate groups comprising 1 to 30 carbons, and ether groupscomprising 1 to 30 carbons,

each Q′ group independently represents a monovalent radical selectedfrom the group consisting of hydrogen, a second functional groupselected from the group consisting of a carbonates other thanpentafluorophenyl carbonate, carbamates, and thiocarbonates, halides,alkyl groups comprising 1 to 30 carbons, alkene groups comprising 1 to30 carbons, alkyne groups comprising 1 to 30 carbons, aryl groupscomprising 6 to 30 carbons, ester groups comprising 1 to 30 carbons,amide groups comprising 1 to 30 carbons, thioester groups comprising 1to 30 carbons, urea groups comprising 1 to 30 carbons, carbamate groupscomprising 1 to 30 carbons, ether groups comprising 1 to 30 carbons, andalkoxy groups comprising 1 to 30 carbons, and any of the foregoing Q′groups substituted with a second functional group selected from thegroup consisting of a carbonates other than pentafluorophenyl carbonate,carbamates, and thiocarbonates,

each X″ is a divalent radical independently selected from the groupconsisting of —O—, —S—, —N(H)—, and —N(R³)—,

each R² and R³ is independently a monovalent radical comprising 1 to10,000 carbons, and

the second cyclic carbonyl compound contains no pentafluorophenyl estergroup and no pentafluorophenyl carbonate group.

In an embodiment, each W′ is —O— (i.e., the second cyclic carbonylcompound is a cyclic carbonate). In another embodiment, the Q′ groupattached to the carbon 5 in formula (8) is ethyl or methyl, and allother Q′ groups are hydrogen. In another embodiment, carbon 5 in formula(8) is an asymmetric center, and the cyclic carbonyl compound comprisesthe (R) or (S) isomer in greater than 80% enantiomeric excess.

Even more specific second cyclic carbonyl compounds derived from thefirst cyclic carbonyl monomer are cyclic carbonates of the generalformula (9):

wherein

m and n are each independently 0 or an integer from 1 to 11, wherein mand n cannot together be 0; and m+n equals an integer from 1 to 11,

L′ represents a single bond or a divalent linking group selected fromthe group consisting of alkyl groups comprising 1 to 30 carbons, alkenegroups comprising 1 to 30 carbons, alkyne groups comprising 1 to 30carbons, aryl groups comprising 6 to 30 carbons, ester groups comprising1 to 30 carbons, amide groups comprising 1 to 30 carbons, thioestergroups comprising 1 to 30 carbons, urea groups comprising 1 to 30carbons, carbamate groups comprising 1 to 30 carbons, and ether groupscomprising 1 to 30 carbons;

R¹ is a monovalent radical selected from the group consisting ofhydrogen, halides, and alkyl groups comprising 1 to 30 carbons;

each X″ is a divalent radical independently selected from the groupconsisting of —O—, —S—, —N(H)—, and —N(R³)—; and

each R² and R³ is independently a monovalent radical comprising 1 to10,000 carbons; and

the second cyclic carbonyl compound contains no pentafluorophenyl estergroup and no pentafluorophenyl carbonate group.

The reaction to form the second functional group occurs withoutdisruption of the cyclic carbonyl moiety, in particular the cycliccarbonate moiety, of the first cyclic carbonyl compound. The byproductof the displacement reaction, pentafluorophenol, can be recovered andrecycled, typically in high yield. The second cyclic carbonate compoundsare potentially capable of forming ROP polycarbonates and other polymersby ROP methods. The ROP polymers can have unique pendant functionalitiesand properties due to the wide variety of available materials for thependant —X″—R² group in formula (7), formula (8), and formula (9).

The method (Method 2) of preparing a second cyclic carbonyl compoundcomprises agitating a mixture comprising the first cyclic carbonylcompound comprising a pentafluorophenyl carbonate group; an optionalsolvent; an optional catalyst; and a nucleophile selected from the groupconsisting of alcohols, amines, and thiols, thereby forming a secondcyclic carbonyl monomer and pentafluorophenol byproduct, wherein thesecond cyclic carbonyl monomer comprises a second functional groupselected from the group consisting of carbonates other thanpentafluorophenyl carbonate, carbamates, and thiocarbonates formed by areaction of the pentafluorophenyl carbonate group with the nucleophile.

As one example, TMCPFP can be converted to the corresponding methylcarbonate TMCMe, according to Scheme 6.

Non-limiting examples of other alcohols capable of reacting with thepentafluorophenyl carbonate of the first cyclic carbonyl monomer withoutaltering the cyclic carbonyl group include:

i-PrOH,

C₆H₅CH₂OH,

Non-limiting examples of amines capable of reacting with thepentafluorophenyl carbonate of TMCPFP to form a pendant carbamate,without altering the cyclic carbonate group, include:

dimethylamine, andisopropylamine.

Non-limiting examples of thiols capable of reacting with the pendant PFPcarbonate to form a pendant thiocarbonate without altering the cycliccarbonyl group include: methane thiol, ethane thiol, phenylthiol, benzylthiol, and the like.

In general, the efficacy of the substitution reactions proceed inaccordance with the nucleophilicity of the nucleophiles. For example,stronger nucleophiles such as primary amines are more effective thanweaker nucleophiles such as primary alcohols. In another example,primary and secondary alcohols can be more effective nucleophiles thansterically hindered alcohols such as tert-butanol in a reaction with thependant pentafluorophenyl carbonate group.

The nucleophile comprising the alcohol, amine, thiol, or combinationsthereof can be attached to larger structures including oligomers,polymers, biomacromolecules, particles, and functionalized surfaces.Non-limiting polymeric structures include linear, branched,hyperbranched, cyclic, dendritic, block, graft, star, and other knownpolymer structures. Non-limiting biomacromolecules include proteins,DNA, RNA, lipids, phospholipids. The particles can have dimensionsranging from less than 1 nanometer to hundreds of micrometers incircular cross-sectional diameter. Non-limiting large particles includesilica, alumina, and polymeric resins such as those commonly used forchromatography and functionalized polymeric beads such as those commonlyused for solid-phase synthesis. Non-limiting nanoparticles include bothorganic and inorganic nanoparticles including those functionalized withligands or stabilizing polymers. Non-limiting organic nanoparticles caninclude crosslinked polymeric nanoparticles, dendrimers, and starpolymers. Non-limiting inorganic nanoparticles include metallicnanoparticles (e.g., gold, silver, other transition metals, and Group 13to Group 16 metals of the periodic table), oxide nanoparticles (e.g.,alumina, silica, hafnia, zirconia, zinc oxide), nitride nanoparticles(e.g., titanium nitride, gallium nitride), sulfide nanoparticles (e.g.,zinc sulfide) semiconducting nanoparticles (e.g., cadmium selenide).Non-limiting functionalized surfaces include surfaces functionalizedwith self-assembled monolayers.

The nucleophile in Method 2 can be a polymeric alcohol. The polymericalcohol can comprise from 4 to 10000 carbons. In one example, thenucleophile is a polyether alcohol, and the pentafluorophenyl carbonategroup of the first cyclic carbonyl compound reacts with the polyetheralcohol to form a second cyclic carbonyl containing material comprisinga pendant carbonate linked to a hydrophilic polyether chain.

Non-limiting examples of polymeric alcohols include polyether alcohols,such as polyethylene glycol (PEG), and mono end capped polyethyleneglycol, such as monomethyl endcapped polyethylene glycol (MPEG):

Other polymeric alcohols include polypropylene glycol (PPG) and monoendcapped derivatives thereof, such as monomethyl end cappedpolypropylene glycol (MPPG):

Still other polymeric alcohols include poly(alkylene glycols) offormulas (12), (13), and (14) described further below.

Generally, the first mixture (Method 2) is agitated at a temperature of−78° C. to 100° C., more specifically −20° C. to 50° C., and even morespecifically −10° C. to 30° C. to form the second cyclic carbonylcompound. In an embodiment, agitation to convert the pentafluorophenylcarbonate to a different carbonate, carbamate, or thiocarbonate isconducted at ambient temperature (herein, 17° C. to 30° C.). The firstmixture is agitated for a period of about 1 hour to about 48 hours, moreparticularly about 20 to 30 hours at the reaction temperature. In anembodiment, the first cyclic carbonyl compound and the second cycliccarbonyl compound are each a cyclic carbonate.

Generally, 1.2 to 1.5 equivalents of the nucleophile with respect to thepentafluorophenyl carbonate are used in the substitution reaction. Whena large excess nucleophile is used (e.g., more than 4 equivalents),ring-opening of the cyclic carbonate can occur as a side reaction.

Typically, a solvent is used in Method 2, though a solvent is notrequired. Depending on the solvent, the pentafluorophenol byproduct canin some instances precipitate directly from the reaction mixture as itis formed. The second cyclic carbonyl compound can be isolated using anyknown method of purification, including distillation, chromatography,extraction, precipitation, and recrystallization. Generally, however,the second mixture is concentrated under vacuum and the resultingresidue is then treated with a second solvent in which thepentafluorophenol byproduct is not soluble, such as methylene chloride.The pentafluorophenol byproduct can then be filtered and recovered forrecycling back to PFC. In an embodiment, 90% to 100% of the theoreticalpentafluorophenol byproduct is recovered for recycling back to PFC. Inone variation, the derived second cyclic carbonate compound can beisolated by washing the organic filtrate with a base such as sodiumbicarbonate solution, drying the filtrate with a drying agent such asmagnesium sulfate or sodium sulfate, and evaporating the second solventunder vacuum. In a another variation, the second cyclic carbonylcompound is further purified by column chromatography orrecrystallization. In this manner the second cyclic carbonyl compoundcan be obtained in a yield of about 50% to about 100%, more particularlyabout 70% to 100%, even more particularly about 80% to 100%.

The optional catalyst of Method 2 can be selected from typical catalystsfor transesterifications, conversions of carbonates to carbamates, orconversion of carbonates to thiocarbonates. These include organiccatalysts and inorganic catalysts, in particular the above describedcatalysts, and most specifically cesium fluoride. When used in Method 2,the catalyst can be present in an amount of 0.02 to 1.00 moles per moleof the first cyclic carbonyl compound, more particularly 0.05 to 0.50moles per mole of the first cyclic carbonyl compound, and even moreparticularly 0.15 to 0.25 moles per mole of the first cyclic carbonylcompound.

In an additional embodiment, Method 1 and Method 2 are performedstep-wise in a single reaction vessel, without an intermediate step toisolate the first cyclic carbonyl compound.

The above-described methods provide a controlled process for introducinga wide range of functionality and connectivity into cyclic carbonylcompounds for ring-opening polymerizations. As stated above, the cycliccarbonyl compounds (first and/or second cyclic carbonyl compounds) canbe formed in isomerically pure form, or as racemic mixtures.

More specific second cyclic carbonyl compounds include but are notlimited to the following cyclic carbonate compounds:

wherein R¹ is a monovalent radical selected from the group consisting ofhydrogen, halides, and alkyl groups comprising 1 to 30 carbons, and R⁵is a monovalent radical selected from the group consisting of hydrogen,halides, alkyl groups comprising 1 to 20 carbons, fluorinated alkylgroups comprising 1 to 20 carbons, and acetoxy groups.Method 3. Ring Opening Polymerization

Further disclosed are ROP polymers obtained by a nucleophilic ringopening polymerization of the above described first and second cycliccarbonyl compounds. The ROP polymer comprises a chain fragment derivedfrom the nucleophilic initiator for the ROP polymerization, and a firstpolymer chain linked to the chain fragment. The chain fragment is alsoreferred to herein as the initiator fragment. The initiator fragmentcomprises at least one oxygen, nitrogen, and/or sulfur backboneheteroatom, which is a residue of a respective alcohol, amine, or thiolnucleophilic initiator group of the ROP initiator. The backboneheteroatom is linked to the first end unit of the first polymer chaingrown therefrom. A second end unit of the first polymer chain can be aliving end unit capable of initiating additional ring openingpolymerization, if desired. A living second end unit comprises anucleophilic group selected from the group consisting of hydroxy group,primary amines, secondary amines, and thiol group. Alternatively, thesecond end unit can be endcapped to impart stability to the ROP polymer,as described further below.

It is understood that the initiator fragment has a different structurethan the first end unit of each ROP polymer chain connected thereto.

The ROP initiator can comprise one or more independently chosen alcohol,amine, or thiol nucleophilic initiator groups. Each nucleophilicinitiator group can potentially initiate a ring opening polymerization.Likewise, the initiator fragment comprises at least one backboneheteroatom derived from a nucleophilic initiator group. Each one of thebackbone heteroatoms that is derived from a nucleophilic initiator groupis linked to a ROP polymer chain grown therefrom. Thus, an initiatorcomprising n nucleophilic initiator groups can potentially initiateformation of n independent ROP polymer chains, where n is an integerequal to or greater than 1. As a non-limiting example, a dinucleophilicinitiator comprising two hydroxy groups can initiate ring openingpolymerization at each hydroxy group. The product ROP polymer comprisesan initiator fragment linked to two ROP polymer chains through the twobackbone oxygens derived from the hydroxy initiator groups.

The ROP polymer comprises at least one ROP polymer chain, referred to asthe first polymer chain. The first polymer chain can comprise ahomopolymer, random copolymer, block copolymer, or combinations of theforegoing polymer types. The first polymer chain comprises a firstrepeat unit comprising a backbone functional group selected from thegroup consisting of carbonate, urea, carbamate, thiocarbamate,thiocarbonate, and dithiocarbonate. The first repeat unit furthercomprises a tetrahedral backbone carbon. In an embodiment, thetetrahedral backbone carbon is linked to a first side chain comprising apendant pentafluorophenyl carbonate. In another embodiment, thetetrahedral backbone carbon is linked to a first side chain comprising apendant pentafluorophenyl carbonate, and to a second side chain selectedfrom the group consisting of hydrogen, halides, and alkyl groupscomprising 1 to 30 carbons (e.g., the R¹ group as described in formulas(5) and (6)).

In the following non-limiting examples, R′—XH is a mono-functionalnucleophilic initiator for ring opening polymerization. R′—XH comprisesa monovalent initiator group —XH, wherein X is a divalent group selectedfrom the group consisting of —O—, —NH—, —NR″—, and —S—. No restrictionis placed on the structure of R′ or R″ with the proviso that the ringopening polymerization produces a useful ROP polymer.

When formed from a first cyclic carbonyl compound, the ROP polymercomprises a pendant pentafluorophenyl carbonate group and is referredherein as the first ROP polymer. As one example, the nucleophilic ringopening polymerization of a first cyclic carbonyl monomer of formula (2)initiated by R′—XH produces a first ROP polymer of formula (2A), whichcomprises a first polymer chain and an initiator fragment R′—X—.

Initiator fragment R′—X— is linked to the carbonyl of the first end unitof the first polymer chain through the oxygen, nitrogen or sulfurheteroatom of the X group. A second end unit of the first polymer chainis a living end unit (i.e., —Y—H in formula (2A)), wherein —Y—H is anucleophilic group selected from the group consisting of hydroxy group,primary amine groups, secondary amine groups, and thiol group. Y, Q′,and n′ are defined as above under formula (2); thus, at least one of theQ′ groups and/or Q″ groups (of the Y groups) comprises a pendantpentafluorophenyl carbonate group (—OCO₂C₆F₅). The subscript d′ is aninteger from 1 to 10000. The repeat unit

comprises a backbone functional group selected from the group consistingof carbonate, ureas, carbamates, thiocarbamates, thiocarbonate, anddithiocarbonate, determined by the independent selection of each Ygroup. The first repeat unit further comprises tetrahedral backbonecarbons labeled 4, 5 and 6. Each of these backbone carbons can be linkedto an independent first side chain Q′ group, which can comprise apentafluorophenyl carbonate group. Further, each of these tetrahedralbackbone carbons can be linked to an optional independent second sidechain Q′ group, as defined above under formula (2).

In another example, the nucleophilic ring opening polymerization of afirst cyclic carbonyl monomer of formula (4), initiated by R′—XH,produces a first ROP polymer of formula (4A), which comprises a firstpolymer chain and an initiator fragment R′—X—:

As above, the initiator fragment R′—X— is linked to the carbonyl of thefirst end unit of the first polymer chain by the oxygen, nitrogen orsulfur heteroatom of the X group. Y′, L′, V′, n and m are defined asabove under formula (4). The subscript d′ is an integer from 1 to 10000.The repeat unit

comprises a backbone functional group selected from the group consistingof carbonate, ureas, carbamates, thiocarbamates, thiocarbonate, anddithiocarbonate, determined by the independent selection of each Y′group. Tetrahedral backbone carbon labeled 5 is linked to a first sidechain comprising a pentafluorophenyl carbonate group. Tetrahedralbackbone carbon labeled 5 can optionally be linked to an independentsecond side chain V′ group, as defined above under formula (4).

In another example, the nucleophilic ring opening polymerization of afirst cyclic carbonyl monomer of formula (5), initiated by R′—XH,produces a polycarbonate chain of formula (5A), which comprises a firstpolymer chain comprising a polycarbonate backbone and an initiatorfragment R′—X—:

Initiator fragment R′—X— is linked by the oxygen, nitrogen or sulfurheteroatom of the X group to the carbonyl of the first end unit of thepolycarbonate chain. R¹, L′, V′, m and n are defined as above underformula (5). The subscript d′ is an integer from 1 to 10000. The repeatunit

comprises a backbone carbonate group. Tetrahedral backbone carbonlabeled 5 is linked to a first side chain comprising a pentafluorophenylcarbonate group, and to a second side chain R′ defined above underformula (5). Tetrahedral backbone carbons labeled 4 and 6 canindependently be linked to independent first and second side chain V′groups, as described above under formula (5).

In another example, the nucleophilic ring opening polymerization of afirst cyclic carbonyl monomer of formula (6), initiated by R′—XH,produces a ROP polycarbonate of formula (6A), which comprises a firstpolycarbonate chain and an initiator fragment R′—X—:

Initiator fragment R′—X— is linked by the oxygen, nitrogen or sulfurheteroatom of the X group to the carbonyl of the end unit of thepolycarbonate chain. R¹, L′, m and n are defined as above under formula(6). The subscript d′ is an integer from 1 to 10000. The repeat unit

comprises a backbone carbonate group. Tetrahedral backbone carbonlabeled 5 is linked to a first side chain comprising a pentafluorophenylcarbonate group, and to a second side chain R′ as defined above underformula (6).

The ROP polymer can comprise two or more linked polymer chains.Additionally, each polymer chain can be a homopolymer of a respectivefirst repeat unit, or a copolymer comprising a second repeat unit, thesecond repeat unit comprising a second backbone functional groupselected from the group consisting of ester, carbonate, urea, carbamate,thiocarbamate, thiocarbonate and dithiocarbonate, which is derived froma cyclic carbonyl comonomer. The first polymer chain can be a randomcopolymer or a block copolymer comprising the first and second repeatunits.

Similar considerations apply to ROP polymers prepared from a secondcyclic carbonyl compound, except that the ROP polymer chain does notcomprise a pentafluorophenyl carbonate group or a pentafluorophenylester group. Instead, the ROP polymer comprises a repeat unit comprisinga side chain comprising a carbonate group other than pentafluorophenylcarbonate, carbamate group, or thiocarbonate group derived from thependant pentafluorophenyl carbonate group of the first cyclic carbonylmonomer.

The first and/or second cyclic carbonyl compounds can undergoring-opening polymerization (ROP) to form biodegradable polymers havingdifferent tacticities. Atactic, syndiotactic and isotactic forms of thepolymers can be produced that depend on the cyclic monomer(s), itsisomeric purity, and the polymerization conditions.

The ring opening polymerization (ROP) of the first cyclic carbonylcompound can occur with substantial retention of the pendantpentafluorophenyl carbonate group in the product ROP polymer, which isalso referred to as the first ROP polymer. The first ROP polymercomprises at least one repeat unit comprising a side chain comprising areactive pentafluorophenyl carbonate group. The first ROP polymerfurther comprises a backbone segment derived from the ring opening ofthe first cyclic carbonyl compound, the backbone segment selected fromthe group consisting of polycarbonates, polycarbamates, polyureas,polythiocarbamates, polythiocarbonates, and polydithiocarbonates. Thefirst ROP polymer can further comprise a polyester backbone segment whena cyclic ester (lactone) comonomer is used in the ring openingpolymerization. Each of these repeat structures is shown in Table 2. TheR group in Table 2 is a backbone fragment formed by the carbons of thering containing the cyclic carbonyl group.

TABLE 2 Polyester

Polycarbonate

Polyurea

Polycarbamate

Polythiocarbamate

Polythiocarbonate

Polydithiocarbonate

The method (Method 3) comprises forming a first mixture comprising thefirst cyclic carbonyl compound comprising a pendant pentafluorophenylcarbonate group, a catalyst, an initiator, an accelerator, and anoptional solvent. The first mixture is then agitated with optionalheating to effect ring opening polymerization of the first cycliccarbonyl compound, thereby forming a second mixture containing abiodegradable ROP polymer, while retaining the pendant pentafluorophenylcarbonate group. The ROP polymer comprises a first polymer chain, thefirst polymer chain comprising a first repeat unit, the first repeatunit comprising a side chain comprising a pendant pentafluorophenylcarbonate group. In a specific embodiment, the side chain has thestructure:

wherein the starred bond is linked to a backbone carbon of thebiodegradable first ROP polymer. In another embodiment, the first repeatunit of the first ROP polymer comprises a tetrahedral backbone carbon,the tetrahedral backbone carbon linked to i) a first side chaincomprising a pentafluorophenyl carbonate group, and ii) a second sidechain group comprising a monovalent hydrocarbon radical. The monovalenthydrocarbon radical can comprise from 1 to 30 carbons. Morespecifically, the monovalent hydrocarbon radical is selected from thegroup consisting of methyl, ethyl, propyl, butyl and pentyl.

In an embodiment, the polymer retains at least 50%, and morespecifically at least 75%, and even more specifically at least 90% ofthe pentafluorophenyl carbonate groups relative to the repeat unitsderived from the first cyclic carbonyl compounds.

As a non-limiting example, TMCPFP undergoes ring opening polymerizationin the presence of a suitable catalyst and nucleophilic initiator benzylalcohol to form a first ROP polymer, a polycarbonate (Scheme 7), whereinBnO is an initiator fragment.

In the naming notation used herein for a ROP polymer, 1-[P(Monomer1,Monomer 2, etc.)]_(w), “I” is the initiator, “[P( )]” indicates apolymer chain formed by ring opening polymerization of one or morecyclic carbonyl compounds listed in the parentheses, and w is the numberof nucleophilic initiator groups of the initiator. For example, if theinitiator is benzyl alcohol, the initiator fragment is a benzyloxy group(BnO), and the name of the ROP homopolymer is BnOH-[P(TMCPFP)]. The ROPpolymer can be prepared under mild conditions to achieve high molecularweight and low polydispersity. Additionally, the ROP polymer can havesubstantially no metal contaminant when prepared with an organocatalyst.The wide utility and ease of manufacture of the first cyclic carbonylcompounds (and their corresponding ROP polymers) makes these monomersconsiderably more useful than similar compounds comprising an acylchloride group or a succinimidyl ester group. The efficient method offorming ROP polymers having an active pentafluorophenyl carbonate sidechain group represents a significant advancement in the state of the artin preparing functionalized ROP polymers.

The first mixture can comprise comonomers, including but not limited tocomonomers comprising a functional group selected from the groupconsisting of cyclic ethers, cyclic esters, cyclic carbonates, cyclicureas, cyclic carbamates, cyclic thioureas, cyclic thiocarbonates, andcyclic dithiocarbonates. Exemplary comonomers include: L-lactide,D-lactide, DL-lactide, beta-butyrolactone, delta-valerolactone,epsilon-caprolactone, trimethylene carbonate, methyl5-methyl-2-oxo-1,3-dioxane-5-carboxylate, ethyl5-methyl-2-oxo-1,3-dioxane-5-carboxylate, and other derivatives ofMTC-OH. These and other examples of cyclic carbonyl comonomers arelisted in Table 3.

TABLE 3

The ring opening polymerization is generally conducted in a reactorunder anhydrous conditions and with an inert atmosphere such as nitrogenor argon. The polymerization can be performed by solution polymerizationin an inactive solvent such as benzene, toluene, xylene, cyclohexane,n-hexane, dioxane, chloroform and dichloroethane, or by bulkpolymerization. The ROP reaction temperature can be from 20° C. to 250°C. Generally, the reaction mixture is heated at atmospheric pressure for0.5 to 72 hours to effect polymerization. Subsequently, additionalcyclic carbonyl compound and catalyst can be added to the second mixtureto effect block polymerization if desired.

Exemplary organometallic ROP catalysts include tetramethoxy zirconium,tetra-iso-propoxy zirconium, tetra-iso-butoxy zirconium, tetra-n-butoxyzirconium, tetra-t-butoxy zirconium, triethoxy aluminum, tri-n-propoxyaluminum, tri-iso-propoxy aluminum, tri-n-butoxy aluminum,tri-iso-butoxy aluminum, tri-sec-butoxy aluminum,mono-sec-butoxy-di-iso-propoxy aluminum, ethyl acetoacetate aluminumdiisopropylate, aluminum tris(ethyl acetoacetate), tetraethoxy titanium,tetra-iso-propoxy titanium, tetra-n-propoxy titanium, tetra-n-butoxytitanium, tetra-sec-butoxy titanium, tetra-t-butoxy titanium,tri-iso-propoxy gallium, tri-iso-propoxy antimony, tri-iso-butoxyantimony, trimethoxy boron, triethoxy boron, tri-iso-propoxy boron,tri-n-propoxy boron, tri-iso-butoxy boron, tri-n-butoxy boron,tri-sec-butoxy boron, tri-t-butoxy boron, tri-iso-propoxy gallium,tetramethoxy germanium, tetraethoxy germanium, tetra-iso-propoxygermanium, tetra-n-propoxy germanium, tetra-iso-butoxy germanium,tetra-n-butoxy germanium, tetra-sec-butoxy germanium and tetra-t-butoxygermanium; halogenated compound such as antimony pentachloride, zincchloride, lithium bromide, tin(IV) chloride, cadmium chloride and borontrifluoride diethyl ether; alkyl aluminum such as trimethyl aluminum,triethyl aluminum, diethyl aluminum chloride, ethyl aluminum dichlorideand tri-iso-butyl aluminum; alkyl zinc such as dimethyl zinc, diethylzinc and diisopropyl zinc; tertiary amines such as triallylamine,triethylamine, tri-n-octylamine and benzyldimethylamine; heteropolyacidssuch as phosphotungstic acid, phosphomolybdic acid, silicotungstic acidand alkali metal salt thereof; zirconium compounds such as zirconiumacid chloride, zirconium octanoate, zirconium stearate and zirconiumnitrate. More particularly, the catalyst is zirconium octanoate,tetraalkoxy zirconium or a trialkoxy aluminum compound.

Organocatalysts for the ROP Polymerization.

Other ROP catalysts include metal-free organocatalysts, defined hereinas a catalyst having none of the following metals in the chemicalformula of the organocatalyst: beryllium, magnesium, calcium, strontium,barium, radium, aluminum, gallium, indium, thallium, germanium, tin,lead, arsenic, antimony, bismuth, tellurium, polonium, and metals ofGroups 3 to 12 of the Periodic Table. This exclusion includes ionic andnon-ionic forms of the foregoing metals. Metals of Groups 3 to 12 of thePeriodic Table include scandium, titanium, vanadium, chromium,manganese, iron, cobalt, nickel, copper, zinc, yttrium, zirconium,niobium, molybdenum, technetium, ruthenium, rhodium, palladium, silver,cadmium, lanthanum, cerium, praseodymium, neodymium, promethium,samarium, europium, gadolinium, terbium, dysprosium, holmium, erbium,thulium, ytterbium, lutetium, hafnium, tantalum, tungsten, rhenium,osmium, iridium, platinum, gold, mercury, actinium, thorium,protactinium, uranium, neptunium, plutonium, americium, curium,berkelium, californium, einsteinium, fermium, mendelevium, nobelium,lawrencium, rutherfordium, dubnium, seaborgium, bohrium, hassium,meitnerium, darmstadtium, roentgenium, and copernicium. Organocatalystscan provide a platform to polymers having controlled, predictablemolecular weights and narrow polydispersities, and minimal metalcontamination. Examples of organocatalysts for the ROP of cyclic esters,carbonates and siloxanes are 4-dimethylaminopyridine, phosphines,N-heterocyclic carbenes (NHC), bifunctional aminothioureas,phosphazenes, amidines, guanidines, and fluoroalcohols (such as mono-and bis-hexafluoroisopropanol compounds).

More specific metal-free organocatalysts for the ROP polymerization ofthe first cyclic monomer includeN-(3,5-trifluoromethyl)phenyl-N′-cyclohexyl-thiourea (TU):

Another metal-free organocatalyst comprises at least one1,1,1,3,3,3-hexafluoropropan-2-ol-2-yl (HFP) group. Singly-donatinghydrogen bond catalysts have the formula (10):R²—C(CF₃)₂OH  (10),wherein R² represents a hydrogen or a monovalent radical having from 1to 20 carbons, for example an alkyl group, substituted alkyl group,cycloalkyl group, substituted cycloalkyl group, heterocycloalkyl group,substituted heterocycloalklyl group, aryl group, substituted aryl group,or a combination thereof. Exemplary singly-donating hydrogen bondingcatalysts are listed in Table 4.

TABLE 4

Doubly-donating hydrogen bonding catalysts have two HFP groups,represented by the general formula (11):

wherein R³ is a divalent radical bridging group containing from 1 to 20carbons, such as an alkylene group, a substituted alkylene group, acycloalkylene group, a substituted cycloalkylene group, aheterocycloalkylene group, substituted heterocycloalkylene group, anarylene group, a substituted arylene group, or a combination thereof.Representative double hydrogen bonding catalysts of formula (11) includethose listed in Table 5. In a specific embodiment, R² is an arylene orsubstituted arylene group, and the HFP groups occupy positions meta toeach other on the aromatic ring.

TABLE 5

In one embodiment, the catalyst is selected from the group consisting of4-HFA-St, 4-HFA-Tol, HFTB, NFTB, HPIP, 3,5-HFA-MA, 3,5-HFA-St, 1,3-HFAB,1,4-HFAB, and combinations thereof.

In particular, catalysts bearing 1,3-bis-HFP aromatic groups (such as1,3-HFAB) were found to be efficient in catalyzing the ROP of TMCPFPwithout concomitant reaction of the pentafluorophenyl carbonate sidechain.

Also contemplated are catalysts comprising HFP-containing groups boundto a support. In one embodiment, the support comprises a polymer, acrosslinked polymer bead, an inorganic particle, or a metallic particle.HFP-containing polymers can be formed by known methods including directpolymerization of an HFP-containing monomer (for example, themethacrylate monomer 3,5-HFA-MA or the styryl monomer 3,5-HFA-St).Functional groups in HFP-containing monomers that can undergo directpolymerization (or polymerization with a comonomer) include acrylate,methacrylate, alpha, alpha, alpha-trifluoromethacrylate,alpha-halomethacrylate, acrylamido, methacrylamido, norbornene, vinyl,vinyl ether, and other groups known in the art. Typical examples of suchpolymerizeable HFP-containing monomers may be found in: Ito et al.,Polym. Adv. Technol. 2006, 17(2), 104-115; Ito et al., Adv. Polym. Sci.2005, 172, 37-245; Ito et al., US20060292485; Maeda et al.,WO2005098541; Allen et al., US20070254235; and Miyazawa et al.,WO2005005370. Alternatively, pre-formed polymers and other solid supportsurfaces can be modified by chemically bonding an HFP-containing groupto the polymer or support via a linking group. Examples of such polymersor supports are referenced in M. R. Buchmeiser, ed. “Polymeric Materialsin Organic Synthesis and Catalysis,” Wiley-VCH, 2003; M. Delgado and K.D. Janda “Polymeric Supports for Solid Phase Organic Synthesis,” Curr.Org. Chem. 2002, 6(12), 1031-1043; A. R. Vaino and K. D. Janda “SolidPhase Organic Synthesis: A Critical Understanding of the Resin”, J.Comb. Chem. 2000, 2(6), 579-596; D. C. Sherrington “Polymer-supportedReagents, Catalysts, and Sorbents: Evolution and Exploitation—APersonalized View,” J. Polym. Sci. A. Polym. Chem. 2001, 39(14),2364-2377; and T. J. Dickerson et al., “Soluble Polymers as Scaffold forRecoverable Catalysts and Reagents,” Chem. Rev. 2002, 102(10),3325-3343. Examples of linking groups include C₁-C₁₂ alkyl, C₁-C₁₂heteroalkyl, an ether group, a thioether group, an amino group, an estergroup, an amide group, or a combination thereof. Also contemplated arecatalysts comprising charged HFP-containing groups bound by ionicassociation to oppositely charged sites on a polymer or a supportsurface.

The ROP reaction mixture comprises at least one catalyst and, whenappropriate, several catalysts together. The ROP catalyst is added in aproportion of 1/20 to 1/40,000 moles relative to the cyclic compounds,and preferably of 1/1,000 to 1/20,000 moles.

Accelerators for ROP Polymerizations.

A nitrogen base can serve as catalyst or as an optional accelerator fora catalyst in a ring opening polymerization. Exemplary nitrogen basesare listed below and include pyridine (Py), N,N-dimethylaminocyclohexane(Me₂NCy), 4-N,N-dimethylaminopyridine (DMAP), trans1,2-bis(dimethylamino)cyclohexane (TMCHD),1,8-diazabicyclo[5.4.0]undec-7-ene (DBU),1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD),7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD), (−)-sparteine, (Sp)1,3-bis(2-propyl)-4,5-dimethylimidazol-2-ylidene (Im-1),1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene (Im-2),1,3-bis(2,6-di-1-propylphenyl(imidazol-2-ylidene (Im-3),1,3-bis(1-adamantyl)imidazol-2-ylidene (Im-4),1,3-di-1-propylimidazol-2-ylidene (Im-5),1,3-di-t-butylimidazol-2-ylidene (Im-6),1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene (Im-7),1,3-bis(2,6-di-1-propylphenyl)-4,5-dihydroimidazol-2-ylidene,1,3-bis(2,6-di-1-propylphenyl)-4,5-dihydroimidazol-2-ylidene (Im-8) or acombination thereof, shown in Table 6.

TABLE 6

In an embodiment, the accelerator has two or three nitrogens, eachcapable of participating as a Lewis base, as for example in thestructure (−)-sparteine. Stronger bases generally improve thepolymerization rate. In some instances, the nitrogen base is the solecatalyst in a ring opening polymerization, such as1,8-diazabicyclo[5.4.0]undec-7-ene (DBU).

Initiators for the ROP Polymerization.

The ROP reaction mixture also comprises an initiator. As stated above,initiators generally include nucleophiles (e.g., alcohols, amines, andthiols). The initiator can be monofunctional, difunctional ormultifunctional such as dendritic, polymeric or related architectures.Monofunctional initiators can include nucleophiles with protectedfunctional groups that include thiols, amines, acids and alcohols. Atypical initiator is phenol or benzyl alcohol.

More particularly, the initiator for the ring opening polymerization ofthe first cyclic carbonyl compound bearing a pendant pentafluorophenylcarbonate is an alcohol. The alcohol initiator can be any suitablealcohol, including mono-alcohol, diol, triol, or other polyol, with theproviso that the choice of alcohol does not adversely affect thepolymerization yield, polymer molecular weight, and/or the desirablemechanical and physical properties of the resulting first ROP polymer.The alcohol can be multi-functional comprising, in addition to one ormore hydroxy groups, a halide, an ether group, an ester group, an amidegroup, or other functional group. Additional exemplary alcohols includemethanol, ethanol, propanol, butanol, pentanol, amyl alcohol, caprylalcohol, nonyl alcohol, decyl alcohol, undecyl alcohol, lauryl alcohol,tridecyl alcohol, myristyl alcohol, pentadecyl alcohol, cetyl alcohol,heptadecyl alcohol, stearyl alcohol, nonadecyl alcohol and otheraliphatic saturated alcohols, cyclopentanol, cyclohexanol,cycloheptanol, cyclooctanol and other aliphatic cyclic alcohols; phenol,substituted phenols, benzyl alcohol, substituted benzyl alcohol,benzenedimethanol, trimethylolpropane, a saccharide, poly(ethyleneglycol), propylene glycol, alcohol functionalized block copolymersderived from oligomeric alcohols, alcohol functionalized branchedpolymers derived from branched alcohols, or a combination thereof.Monomeric diol initiators include ethylene glycols, propylene glycols,hydroquinones, and resorcinols. An example of a diol initiator is BnMPA,derived from 2,2-dimethylol propionic acid, a precursor used in thepreparation of cyclic carbonate monomers.

More particular polymeric alcohol initiators are polyether alcohols,such as a poly(alkylene glycol) or a mono end capped poly(alkyleneglycol) which includes but is not limited to poly(alkylene glycol)s andmono end capped poly(alkylene glycol)s. Such initiators serve tointroduce a main chain hydrophilic first block into the resulting firstROP polymer. A second block of the ROP polymer comprises a living chainsegment comprising a side chain pentafluorophenyl carbonate group, theliving chain segment formed by ring opening polymerization of a firstcyclic carbonyl compound.

The polyether alcohol can be a poly(alkylene glycol) of the generalformula (12):HO—[C(R⁷)₂(C(R⁷)₂)_(a′)C(R⁷)₂O]_(n)—H  (12),Wherein a′ is 0 to 8, n is an integer from 2 to 10000, and each R⁷ isindependently a monovalent radical consisting of hydrogen and an alkylgroup of 1 to 30 carbons. Thus, the ether repeat unit comprises 2 to 10backbone carbons between each backbone oxygen. More particularly, thepoly(alkylene glycol) can be a mono end capped poly(alkylene glycol),represented by the formula (13):R⁸O—[C(R⁷)₂(C(R⁷)₂)_(a′)C(R⁷)₂O]_(n)—H  (13),wherein R⁸ is a monovalent hydrocarbon radical comprising 1 to 20carbons.

As non-limiting examples, the polyether alcohol can be a poly(ethyleneglycol) (PEG), having the structure HO—[CH₂CH₂O]_(n)—H, wherein theether repeat unit CH₂CH₂O (shown in the brackets) comprises two backbonecarbons linked to a backbone oxygen. The polyether alcohol can also be apolypropylene glycol) (PPG) having the structure HO—[CH₂CH(CH₃)O]_(n)—H,where the ether repeat unit CH₂CH(CH₃)O comprises two backbone carbonslinked to a backbone oxygen with a methyl side-chain. An example of monoend capped PEG is the commercially available mono methyl end capped PEG(MPEG), wherein R⁸ is a methyl group. Other examples includepoly(oxetane), having the structure HO—[CH₂CH₂CH₂O]_(n)—H, andpoly(tetrahydrofuran), having the structure HO—[CH₂(CH₂)₂CH₂O]_(n)—H.

The mono end capped poly(alkylene glycol) can comprise more elaboratechemical end groups, represented by the general formula (14):Z″—[C(R⁷)₂(C(R⁷)₂)_(a′)C(R⁷)₂O]_(n-1)—H  (14),wherein Z″ is a monovalent radical including the backbone carbons andoxygen of the end repeat unit, and can have 2 to 100 carbons. Thefollowing non-limiting examples illustrate mono end-derivatization ofpoly(ethylene glycol) (PEG). As described above, one end repeat unit ofPEG can be capped with a monovalent hydrocarbon group having 1 to 20carbons, such as the mono methyl PEG (MPEG), wherein Z″ is MeOCH₂CH₂O—.The dash on the end of the MeOCH₂CH₂O— indicates the point of attachmentto the polyether chain. In another example, Z″ includes a thiol group,such as HSCH₂CH₂O—, or a thioether group, such as MeSCH₂CH₂O—. Inanother example, one end unit of PEG is an aldyhyde, wherein Z″ can beOCHCH₂CH₂O—. Treating the aldehyde with a primary amine produces animine, wherein Z″ is R⁹N═CHCH₂CH₂O—. R⁹ is a monovalent radical selectedfrom hydrogen, an alkyl group of 1 to 30 carbons, or an aryl groupcomprising 6 to 100 carbons. Continuing, the imine can be reduced to anamine, wherein Z″ is R⁹NHCH₂CH₂CH₂O—. In another example, one end repeatunit of PEG can be oxidized to a carboxylic acid, wherein Z″ isHOOCCH₂O—. Using known methods the carboxylic acid can be converted toan ester, wherein Z″ becomes R⁹OOCCH₂O—. Alternatively, the carboxylicacid can be converted to an amide, wherein Z″ becomes R⁹NHOCCH₂O—. Manyother derivatives are possible. In a particular embodiment, Z″ is agroup comprising a biologically active moiety that interacts with aspecific cell type. For example, the Z″ group can comprise a galactosemoiety which specifically recognizes liver cells. In this instance, Z″has the structure:

wherein L″ is a divalent linking group comprising 2 to 50 carbons. Thehyphen on the right side of L″ indicates the attachment point to thepolyether chain. Z″ can comprise other biologically active moieties suchas a mannose moiety.

The ring-opening polymerization can be performed with or without the useof a solvent, more particularly with a solvent. Optional solventsinclude dichloromethane, chloroform, benzene, toluene, xylene,chlorobenzene, dichlorobenzene, benzotrifluoride, petroleum ether,acetonitrile, pentane, hexane, heptane, 2,2,4-trimethylpentane,cyclohexane, diethyl ether, t-butyl methyl ether, diisopropyl ether,dioxane, tetrahydrofuran, or a combination comprising one of theforegoing solvents. When a solvent is present, a suitable cycliccarbonyl compound concentration is about 0.1 to 5 moles per liter, andmore particularly about 0.2 to 4 moles per liter. In a specificembodiment, the reaction mixture for the ring-opening polymerizationcontains no solvent.

The ring-opening polymerization of the first and/or second cycliccarbonyl monomer can be performed at a temperature that is about ambienttemperature or higher, more specifically a temperature from 15° C. to200° C., and more particularly 20° C. to 60° C. Reaction times vary withsolvent, temperature, agitation rate, pressure, and equipment, but ingeneral the polymerizations are complete within 1 to 100 hours.

Whether performed in solution or in bulk, the polymerizations areconducted in an inert (e.g., dry) atmosphere and at a pressure of from100 to 500 MPa (1 to 5 atm), more typically at a pressure of 100 to 200MPa (1 to 2 atm). At the completion of the reaction, the solvent can beremoved using reduced pressure.

The optional nitrogen base accelerator, when present, is present in anamount of 0.1 to 5.0 mol %, 0.1 to 2.5 mol %, 0.1 to 1.0 mol %, or 0.2to 0.5 mol %, based on total moles of cyclic carbonyl compound.

The amount of initiator is calculated based on the equivalent molecularweight per nucleophilic initiating group in the initiator (e.g., hydroxygroups). The initiating groups are present in an amount of 0.001 to 10.0mol %, 0.1 to 2.5 mol %, 0.1 to 1.0 mol %, and 0.2 to 0.5 mol %, basedon total moles of cyclic carbonyl compound. For example, if themolecular weight of the initiator is 100 g/mole and the initiator has 2hydroxy groups, the equivalent molecular weight per hydroxy group is 50g/mole. If the polymerization calls for 5 mol % hydroxy groups per moleof monomer, the amount of initiator is 0.05×50=2.5 g per mole ofmonomer.

In a specific embodiment, the ring opening catalyst is present in anamount of about 0.2 to 20 mol %, the optional accelerator is present inan amount of 0.1 to 5.0 mol %, and the hydroxy groups of the initiatorare present in an amount of 0.1 to 5.0 mol % based on the equivalentmolecular weight per nucleophilic initiator group in the initiator.

The ring opening polymerization forms a ROP polymer comprising a livingpolymer chain. The living polymer chain can comprise a terminal hydroxygroup, terminal thiol group, or terminal amine group, each of which caninitiate further ROP chain growth, if desired. At least one repeat unitof the ROP polymer comprises a side chain pentafluorophenyl carbonategroup.

The ROP polymer can comprise a linear polymer, a cyclic polymer, a graftcopolymer, and other polymer topologies. The ROP polymer can be a randomcopolymer, an alternating copolymer, a gradient copolymer, or a blockcopolymer. Block copolymerization may be achieved by sequentiallypolymerizing different cyclic carbonyl monomers or by simultaneouslycopolymerizing monomers with the appropriate reactivity ratios. The ROPpolymer can comprise hydrophilic repeat units, hydrophobic repeat units,and combinations thereof, thereby imparting amphiphilic properties tofirst ROP polymer. In an embodiment, the ROP polymer has a backbonecomprising a polycarbonate homopolymer, a polycarbonate copolymer, or apolyestercarbonate copolymer.

In a preferred embodiment, the catalyst, accelerator, and reactionconditions are selected such that the growing chain end (a nucleophilicalcohol) will not react intramolecularly with a pendantpentafluorophenyl carbonate group of the same polymer chain to form acyclic structure, or intermolecularly with a pendant pentafluorophenylcarbonate group of another polymer chain. In this way, linear polymerswith controlled polydispersities can be synthesized. At high conversionswhen the relative concentration of monomer is low, reaction with pendantpentafluorophenyl carbonate groups can occur with subsequent broadeningof the polydispersity.

If the reaction conditions permit (e.g., when a strongly activatingcatalyst is used), the growing chain end (e.g., a nucleophilic alcohol)can react with the pendant pentafluorophenyl carbonate side chain groupof an unreacted first cyclic carbonate monomer or a pendantpentafluorophenyl carbonate side chain group of the same (i.e., anintramolecular reaction) or another polymer chain (i.e., anintermolecular reaction). Reaction with a pendant pentafluorophenylcarbonate side chain group of an unreacted first cyclic carbonatemonomer will result in the formation of a macromer, which cansubsequently be polymerized to make a comb or graft polymer.Intramolecular reaction can produce a cyclic structure, whileintermolecular reaction can afford a branched polymer. If stronglyforcing reaction conditions are used, the growing chain end can alsoreact with the carbonyl group (e.g. ester, carbonate . . . etc.) of thepolymer main chain and lead to macrocyclization or segmental exchange(by transesterification for example). Such conditions should be avoidedif one wants to produce polymers with controlled molecular weights andpolydispersities.

Alternatively, if a comonomer comprising additional nucleophilic groups(e.g., OX-BHMP) is used in the preparation of the first ROP polymercomprising a pentafluorophenyl carbonate side chain group, then theseadditional nucleophilic groups can serve as initiator groups (whichinitiate polymer chains), as well as nucleophilic groups that can reactwith the pendant pentafluorophenyl carbonate side chain groups. If theadditional nucleophilic groups only serve as initiator groups, theresult of the synthesis can be a first ROP polymer comprising apentafluorophenyl carbonate side chain group with a branched,hyperbranched, comb, bottlebrush, or other such structure. If thereaction conditions permit, the additional nucleophilic groups can alsoreact with the pendant pentafluorophenyl carbonate side chain groups ofan unreacted first cyclic carbonate monomer or a pendantpentafluorophenyl carbonate side chain group of the same (i.e., anintramolecular reaction) or another polymer chain (i.e., anintermolecular reaction). Intramolecular reaction can produce a cyclicstructure, while intermolecular reaction can afford a polymericcrosslinked network or gel (which might or might not have any residualpentafluorophenyl carbonate side chain groups remaining). Again,strongly forcing reaction conditions can allow these nucleophilic groupsto also react with the carbonyl groups (e.g. ester, carbonate . . .etc.) of the polymer main chains, although this is generallyundesirable.

The first ROP polymer can be a homopolymer, copolymer, or blockcopolymer. The polymer can have a number-average molecular weight ofusually 1,000 to 200,000, more particularly 2,000 to 100,000, and stillmore particularly 5,000 to 80,000. In an embodiment, the first ROPpolymer chain has a number average molecular weight M_(n) of 10000 to20000 g/mole. The first ROP polymer chains can also have a narrowpolydispersity index (PDI), generally from 1.01 to 1.35, moreparticularly 1.1 to 1.30, and even more particularly 1.1 to 1.25.

Method 4. Functionalization of the First ROP Polymer.

Further disclosed is a method (Method 4) of converting the first ROPpolymer into a functionalized second polymer by reaction of the pendantpentafluorophenyl carbonate side chain group of the first ROP polymerwith a suitable nucleophile. The method can be performed using mildconditions, without disruption of the backbone carbonyl groups of thefirst ROP polymer. As a non-limiting example, the functionalization offirst ROP polymer BnOH-[P(MTCPFP)] using nucleophile R″—XH isillustrated in Scheme 8.

R″—XH is a nucleophile selected from the group consisting of alcohols,amines, thiols, and combinations thereof, wherein R″ is withoutrestriction with the proviso that a useful polymer is obtained. In anembodiment, R″ comprises 1 to 10000 carbons. The functionalized secondpolymer can be prepared having essentially no remainingpentafluorophenyl carbonate groups.

The method (Method 4) comprises forming a first mixture comprising thefirst ROP polymer comprising a pentafluorophenyl carbonate side chaingroup, an optional second catalyst, a nucleophile selected from thegroup consisting of alcohols, amines, thiols, and combinations thereof,and an optional solvent. The first mixture is agitated and optionallyheated to effect reaction of the pentafluorophenyl carbonate group withthe nucleophile, thereby forming a functionalized second polymercomprising a pendant functional group selected from the group consistingof carbonates other than a pentafluorophenyl carbonate, carbamates,thiocarbonates, and combinations thereof, and pentafluorophenolbyproduct.

The first ROP polymer can be treated with a variety of nucleophiles toform a functionalized second polymer. Exemplary nucleophiles include butare not limited to polymeric and non-polymeric alcohols, thiols, andamines described further above under Method 2 and Method 3. When thenucleophile is a polyether alcohol, the functionalized second polymercomprises a side chain carbonate group comprising a hydrophilicpolyether chain.

The nucleophile can further comprise isotopically enriched versions ofcarbon, nitrogen and hydrogen, including for example ¹³C, ¹⁴C, ¹⁵N,deuterium, or combinations thereof. The amine can also comprise aradioactive moiety including a heavy metal radioactive isotope. Method 2described above can also include a nucleophile comprising isotopicallyenriched versions of carbon, nitrogen, and hydrogen, as well as aradioactive moiety.

The nucleophile can further comprise additional reactive functionalgroups including hydroxy, amino, thiol, vinyl, allyl, propargyl,acetylene, azide, glycidyl, furan, furfuryl, acrylate, methacrylate,vinyl phenyl, vinyl ketone, vinyl ether, crotyl, fumarate, maleate,maleimide, butadiene, cyclopentadiene, cyclohexadiene, and derivativesthereof. These additional reactive groups may serve as sites foradditional subsequent modification through Diels-Alder or Huisgen1,3-dipolar cycloadditions, for example.

The nucleophile comprising an alcohol group, amine group, thiol group,or combination thereof can be attached to a larger structure includingoligomers, polymers, biomacromolecules, particles, and functionalizedsurfaces. Non-limiting oligomeric and polymeric structures includelinear, branched, hyperbranched, cyclic, dendrimeric, block, graft,star, and other known polymer structures. Non-limiting biomacromoleculesinclude carbohydrates, proteins, DNA, RNA, lipids, phospholipids.Particles comprising the nucleophilic groups can have an averagediameter ranging from less than 1 nanometer to hundreds of micrometers.Non-limiting functionalized surfaces include silica, alumina, andpolymeric resins such as those commonly used for chromatography andfunctionalized polymeric beads such as those commonly used forsolid-phase synthesis.

When multifunctional nucleophiles are used (e.g., diamines, triamines,diols, triols, or aminoalcohols), the functionalization reaction canresult in the formation of a functionalized second polymer comprising acrosslinked network or gel. The multifunctional nucleophile can therebyserve as a crosslinking agent by reacting with pentafluorophenylcarbonate groups from different polymer chains.

Nanoparticulate nucleophiles comprising an alcohol, amine, thiol, orcombination thereof, can have an average diameter of from 1 nm to 500nm. The nanoparticles can comprise both organic and inorganicnanoparticles, including those functionalized with ligands orstabilizing polymers. Organic nanoparticles can include, but are notlimited to, crosslinked polymeric nanoparticles, dendrimers, and starpolymers. Inorganic nanoparticles include but are not limited tometallic nanoparticles (e.g., gold, silver, other transition metals, andGroup 13 to Group 16 metals of the Periodic Table), oxide nanoparticles(e.g., alumina, silica, hafnia, zirconia, zinc oxide), nitridenanoparticles (e.g., titanium nitride, gallium nitride), sulfidenanoparticles (e.g., zinc sulfide) semiconducting nanoparticles (e.g.,cadmium selenide). Functionalized surfaces include, but are not limitedto, surfaces functionalized with self-assembled monolayers.

The reaction of the first ROP polymer with a nucleophile is generallyconducted in a reactor under a dry inert atmosphere such as nitrogen orargon. The reaction can be performed using an inactive solvent such asbenzene, toluene, xylene, dioxane, chloroform and dichloroethane,methylene chloride, tetrahydrofuran, acetonitrile, N,N-dimethylformamide, dimethylsulfoxide, dimethyl acetamide, or mixtures thereof.The functionalization reaction temperature can be from 20° C. to 250° C.Generally, the reaction mixture is agitated at room temperature andatmospheric pressure for 0.5 to 72 hours to effect complete conversionof the pentafluorophenyl carbonate groups. Subsequently, an additionalnucleophile and catalyst can be added to the second mixture to effectfurther functionalization of any non-reacted pentafluorophenyl carbonategroups. Alternatively, an additional nucleophile and coupling reagentcan be added to the second mixture to effect functionalization of anyhydroxy groups that have formed by hydrolysis of the pendantpentafluorophenyl carbonate groups.

Typically, the first mixture comprises a solvent, although this is notrequired. Depending on the solvent, the pentafluorophenol byproduct canin some instances precipitate directly from the reaction mixture as itis formed. Generally, however, the functionalized second polymer can beisolated by precipitation using a suitable non-solvent such asisopropanol. In this manner the functionalized second polymer can beobtained in a yield of about 50% to about 100%, more particularly about70% to 100%, even more particularly about 80% to 100%.

The optional catalyst of the first mixture (Method 4) can be selectedfrom typical catalysts for transesterifications, conversions of estersto amides, or conversion of esters to thioesters. These include organiccatalysts and inorganic catalysts, in particular the above describedcatalysts, and most specifically cesium fluoride. When used in the firstmixture, the catalyst can be present in an amount of 0.02 to 1.00 molesper mole of cyclic carbonyl monomer used to prepare the first ROPpolymer, more particularly 0.05 to 0.50 moles per mole of the cycliccarbonyl monomer used to prepare the first ROP polymer, and even moreparticularly 0.15 to 0.25 moles per mole of the cyclic carbonyl monomerused to prepare the ROP polymer.

In an additional embodiment, the polymerization to form the first ROPpolymer (Method 3) comprising a pendant pentafluorophenyl carbonategroup, and the subsequent reaction of the first ROP polymer with anucleophile to form a functionalized second polymer (Method 4) bydisplacement of the pentafluorophenoxy group of the pendantpentafluorophenyl carbonate, are conducted step-wise in a singlereaction vessel, without an intermediate step to isolate the first ROPpolymer bearing the side chain pentafluorophenyl carbonate group.

The above-described methods provide a controlled process for introducinga wide range of functionality and connectivity into polymers formed byring-opening polymerizations of cyclic carbonyl compounds comprising apendant pentafluorophenyl carbonate group. The first ROP polymer and thefunctionalized second polymer are particularly advantageous because theycan be obtained with minimal metal contaminant when produced by anorganocatalyst whose chemical formula has none of the following metals:beryllium, magnesium, calcium, strontium, barium, radium, aluminum,gallium, indium, thallium, germanium, tin, lead, arsenic, antimony,bismuth, tellurium, polonium, and metals of Groups 3 to 12 of thePeriodic Table.

In preferred embodiments, the first ROP polymer and/or thefunctionalized second polymer contains no more than 1000 ppm (parts permillion), preferably no more than 100 ppm, more preferably no more than10 ppm, and still more preferably no more than 1 ppm, of everyindividual metal of the group consisting of beryllium, magnesium,calcium, strontium, barium, radium, aluminum, gallium, indium, thallium,germanium, tin, lead, arsenic, antimony, bismuth, tellurium, polonium,and metals of Groups 3 to 12 of the Periodic Table. For example, if thelimit is no more than 100 ppm, then each of the foregoing metals has aconcentration not exceeding 100 ppm in the first ROP polymer, thefunctionalized second polymer, or both. When an individual metalconcentration is below detection capability or has a concentration ofzero parts, the concentration is expressed as 0 ppm. In anotherembodiment, every individual metal of the group consisting of beryllium,magnesium, calcium, strontium, barium, radium, aluminum, gallium,indium, thallium, germanium, tin, lead, arsenic, antimony, bismuth,tellurium, polonium, and metals of Groups 3 to 12 of the Periodic Tablehas a concentration of 0 ppm to 1000 ppm, 0 ppm to 500 ppm, 0 ppm to 100ppm, 0 ppm to 10 ppm, or even more particularly 0 ppm to 1 ppm in thefirst ROP polymer, the functionalized second polymer, or both. Forexample, if the concentration can have a value in the range of 0 ppm to100 ppm (inclusive), then each of the foregoing metals has aconcentration of 0 ppm to 100 ppm in the first ROP polymer, thefunctionalized second polymer, or both. In another embodiment, the firstROP polymer, the functionalized second polymer, or both comprises lessthan 1 ppm of every individual metal of the group consisting ofberyllium, magnesium, calcium, strontium, barium, radium, aluminum,gallium, indium, thallium, germanium, tin, lead, arsenic, antimony,bismuth, tellurium, polonium, and metals of Groups 3 to 12 of thePeriodic Table. To be clear, if the limit is less than 1 ppm, then eachof the foregoing metals has a concentration of less than 1 ppm in thefirst ROP polymer, the functionalized second polymer, or both.

The polymer products of the ROP polymerizations can be applied toconventional molding methods such as compression molding, extrusionmolding, injection molding, hollow molding and vacuum molding, and canbe converted to molded articles such as various parts, receptacles,materials, tools, films, sheets and fibers. A molding composition can beprepared comprising the polymer and various additives, including forexample nucleating agents, pigments, dyes, heat-resisting agents,antioxidants, weather-resisting agents, lubricants, antistatic agents,stabilizers, fillers, strengthened materials, fire retardants,plasticizers, and other polymers. Generally, the molding compositionscomprise 30 wt. % to 100 wt. % or more of the polymer based on totalweight of the molding composition. More particularly, the moldingcomposition comprises 50 wt. % to 100 wt. % of the polymer.

The first ROP polymer and the functionalized second polymer can beformed into free-standing or supported films by known methods.Non-limiting methods to form supported films include dip coating, spincoating, spray coating, doctor blading. Generally, such coatingcompositions comprise 0.01 wt. % to 90 wt. % of the polymer based ontotal weight of the coating composition. More particularly, the moldingcomposition comprises 1 wt. % to 50 wt. % of the polymer based on totalweight of the coating composition. The coating compositions generallyalso include a suitable solvent necessary to dissolve the polymerproduct.

The coating compositions can further include other additives selected soas to optimize desirable properties, such as optical, mechanical, and/oraging properties of the films. Non-limiting examples of additivesinclude surfactants, ultraviolet light absorbing dyes, heat stabilizers,visible light absorbing dyes, quenchers, particulate fillers, and flameretardants. Combinations of additives can also be employed.

The second cyclic carbonyl compounds, particularly cyclic carbonatecompounds can also bear polymerizeable functional groups which can bepolymerized by ROP, free-radical, CRP, or other polymerizationtechniques. For example, monomers TMCEMA (Example 5) and TMCNSt (Example8) bear unsaturated groups which can be polymerized via free radical orcontrolled radical polymerization techniques, includingnitroxide-mediated radical polymerization, atom transfer radicalpolymerization (ATRP), and reversible addition-fragmentationpolymerization (RAFT). These monomers can be polymerized through thecyclic carbonyl group, the polymerizeable functional group, or both. Thecyclic carbonyl group and the polymerizeable functional group can bepolymerized in any order (e.g., ROP of a cyclic carbonate and thenpolymerization of the functional group, vice versa, or simultaneously).Alternatively, the functional group can be polymerized (orcopolymerized) to afford a polymer with pendant cyclic carbonyl groups.These cyclic carbonyl groups can then be reacted to append groups to thepolymer. For example, ring-opening reactions of cyclic carbonates withprimary or secondary amines are well known to produce hydroxycarbamates.

EXAMPLES

Unless indicated otherwise, parts are parts by weight, temperature is in° C. and pressure is at or near atmospheric.Bis(pentafluorophenyl)carbonate was obtained from Central Glass Co.,Ltd. (Japan). All the other starting materials were obtained (inanhydrous grade if possible) from Aldrich Chemical Co. ¹H, ¹³C and ¹⁹Fnuclear magnetic resonance (NMR) spectra were obtained at roomtemperature on a Bruker Avance 400 spectrometer.

The following Example 1 illustrates the method of making a first6-membered cyclic carbonate compound, TMCPFP. Example 2 illustrates themethod of making a first 5-membered cyclic carbonate compound, GLCPFP.Examples 3 to 8 illustrate methods of displacing the PFP carbonate ofTMCPFP to form a variety of second cyclic carbonate compounds comprisingdifferent carbonate or carbamate groups. Example 9 illustrates a methodof displacing the PFP carbonate of GLCPFP to form a second cycliccarbonate compound comprising a carbamate group. Example 10 illustratesthe polymerization of a second cyclic carbonate monomer bearing areactive side group. Example 11 illustrates the polymerization of afirst cyclic carbonate to create a block copolymer. Example 12illustrates the post-polymerization functionalization of the blockcopolymer of Example 11 to afford a polymer with functionalizedcarbamate side groups.

Example 1 Preparation of (5-methyl-2-oxo-1,3-dioxan-5-yl)methylperfluorophenyl carbonate (TMCPFP)

To a 100 mL round bottom flask, 1,1,1-tris(hydroxymethyl)ethane (2.0 g,16.7 mmol) was combined with bis(pentafluorophenyl)carbonate (15.1 g,38.3 mmol, 2.3 eq.) and cesium fluoride (0.76 g, 5.0 mmol, 0.3 eq.) inanhydrous tetrahydrofuran (THF) (11.9 mL) and stirred for four hours atroom temperature. Initially the reaction was heterogeneous, but afterone hour the reaction formed a clear homogeneous solution. The reactionwas concentrated in vacuo (100 mm Hg, 30° C.) and the residue wasdissolved in methylene chloride (˜50 mL). Upon standing (˜10 min), thepentafluorophenol byproduct precipitated from solution and was recoveredby filtration. The mother liquor was washed with aqueous sodiumbicarbonate (3×50 mL) until the pH of aqueous layer was ˜8 and then withbrine (1×50 mL). The organic layer was separated and dried overanhydrous sodium sulfate. The solution was concentrated to give thecrude product that was purified by recrystallization. The crude productwas dissolved in ethyl acetate (24 mL) at 65° C. n-Hexane (35 mL) wasadded at the same temperature, and the resulting solution was allowed tocool to room temperature. After stirring the solution overnight, thewhite crystalline product TMCPFP was separated by filtration (4.0 g, 67%yield). m.p. 130-131° C. ¹H NMR (CDCl₃, 400 Hz) 1.22 (s, 3H), 4.23 (d,2H, J=11 Hz), 4.37 (s, 2H), 4.38 (d, 2H, J=11 Hz). ¹⁹F NMR (CDCl₃, 376Hz) −154.3˜−154.3 (m, 2F), −157.8 (t, 1F, J=22 Hz), −162.6˜−162.7 (m,2F). ¹³C NMR (CDCl₃, 100 Hz) 16.8, 32.6, 70.3, 73.0, 125.4, 137.9,140.1, 141.3, 147.4, 151.1.

Example 2 Preparation of (2-oxo-1,3-dioxolan-4-yl)methyl perfluorophenylcarbonate (GLCPFP)

Glycerin (1.0 g, 0.011 mmol) was combined with bis(pentafluorophenylcarbonate) (9.8 g, 0.025 mmol, 2.3 eq) and CsF (0.49 g, 0.033 mmol, 0.3eq) in THF (15.6 mL) and stirred for 6 hours at room temperature.Initially the reaction was heterogeneous, but after one hour thereaction formed a clear homogeneous solution. The reaction wasconcentrated, and redissolved in methylene chloride. After sitting for10 minutes, the pentafluorophenol byproduct fell out of the solution.After removal of the byproduct by filtration, the mother liquid waswashed brine. The organic layer was separated and dried by NaSO₄. Thesolution was concentrated to give the crude product. The crude wasdissolved with n-hexane (2 mL), and a seed crystal was added to thesolution. After keeping the solution at 0° C. for one hour, the crystalwas separated by filtration (2.97 g, y. 83%).

Example 3 Preparation of ethyl (5-methyl-2-oxo-1,3-dioxan-5-yl)methylcarbonate (TMCEt)

Under a dry nitrogen atmosphere, anhydrous ethanol (0.06 g, 1.26 mmol,1.5 eq.) was added to the solution of TMCPFP (0.3 g, 0.84 mmol) andcesium fluoride (0.038 g, 0.25 mmol, 0.3 eq.) in THF (3 mL). The mixturewas stirred for 1 day at room temperature. After the reaction, thesolution was concentrated in vacuo and redissolved in methylenechloride. Upon standing (˜10 min) the pentafluorophenol byproductprecipitated from solution and was removed by filtration. The crudeproduct was purified by column chromatography (ethylacetate/n-hexane=1/3) to give TMCEt as a white crystalline powder (0.11g, 63% yield). m.p. 68-69° C. ¹H NMR (CDCl₃, 400 Hz) 1.15 (s, 3H), 1.33(t, 3H, J=7 Hz), 4.14 (s, 2H), 4.15 (d, 2H, J=11 Hz), 4.23 (q, 2H, J=7Hz), 4.34 (d, 2H, J=11 Hz). ¹³C NMR (CDCl₃, 100 Hz) 14.2, 16.9, 32.3,64.7, 67.8, 73.3, 147.7, 154.7.

Example 4 Preparation of benzyl (5-methyl-2-oxo-1,3-dioxan-5-yl)methylcarbonate (TMCBn)

Under a dry nitrogen atmosphere, anhydrous benzyl alcohol (0.06 g, 0.55mmol, 1.0 eq.) was added to the solution of TMCPFP (0.2 g, 0.55 mmol)and pyridine (0.04 g, 0.49 mmol, 0.89 eq.) in THF (2 mL). The mixturewas stirred for 3 days at 55° C. After the reaction, the solution wasconcentrated and redissolved in methylene chloride. Upon standing (˜10min) the pentafluorophenol byproduct precipitated from solution. Afterremoval of the byproduct by filtration, the mother liquor was washedwith aqueous sodium bicarbonate (pH of aqueous layer ˜8) and brine. Theorganic layer was separated and dried over anhydrous sodium sulfate. Thesolution was concentrated to give the crude product which was purifiedby recrystallization (toluene/n-hexane 3:1) to give TMCBn as a whitecrystalline powder (0.03 g, 20% yield). m.p. 72-75° C. ¹H NMR (CDCl₃,400 Hz) 1.14 (s, 3H), 4.13 (d, 2H, J=11 Hz), 4.16 (s, 2H), 4.32 (d, 2H,J=11 Hz), 5.18 (s, 2H), 7.38-7.39 (m, 5H). ¹³C NMR (CDCl₃, 100 Hz) 17.0,32.4, 68.1, 70.3, 73.2, 128.6, 128.7, 128.9, 134.6, 147.5, 154.6.

Example 5 Preparation of2-(((5-methyl-2-oxo-1,3-dioxan-5-yl)methoxy)carbonyloxy)ethylmethacrylate (TMCEMA)

Under a dry nitrogen atmosphere, 2-hydroxyethyl methacrylate (0.037 g,0.28 mmol, 1.0 eq.) was added to the solution of TMCPFP (0.1 g, 0.28mmol) and cesium fluoride (0.013 g, 0.084 mmol, 0.3 eq.) in THF (1 mL).The mixture was stirred for 3 days at room temperature. After thereaction, the solution was concentrated and redissolved in methylenechloride. Upon standing (˜10 min) the pentafluorophenol byproductprecipitated from solution and was removed by filtration. The solventwas removed in vacuo to afford a crude product that was further purifiedby column chromatography (ethyl acetate/n-hexane=1/3) to give TMCEMA asa colorless oil (0.03 g, 35% yield). ¹H NMR (CDCl₃, 400 Hz) 1.16 (s,3H), 1.96 (s, 3H), 4.16 (d, 2H, J=11 Hz), 4.17 (s, 2H), 4.34 (d, 2H,J=11 Hz), 3.39-4.43 (m, 2H), 5.63 (bs, 1H), 6.15 (s, 1H). ¹³C NMR(CDCl₃, 100 Hz) 17.0, 18.3, 32.4, 62.0, 66.2, 68.2, 73.2, 126.4, 135.7,147.5, 154.6, 167.1.

Example 6 Preparation of isopropyl(5-methyl-2-oxo-1,3-dioxan-5-yl)methyl carbonate (TMCiPR)

Under a dry nitrogen atmosphere, anhydrous 2-propanol (0.025 g, 0.42mmol, 1.5 eq.) was added to the solution of TMCPFP (0.1 g, 0.28 mmol)and cesium fluoride (0.013 g, 0.084 mmol, 0.3 eq.) in THF (1 mL). Themixture was stirred for 1 day at 55° C. After the reaction, the solutionwas concentrated and redissolved in methylene chloride. Upon standing(˜10 min) the pentafluorophenol byproduct precipitated from solution andwas removed by filtration. The solvent was removed in vacuo to afford acrude product that was further purified by column chromatography (ethylacetate/n-hexane=1/3) to give TMCiPR as a white crystalline powder (0.03g, 46% yield). m.p. 64˜65° C. ¹H NMR (CDCl₃, 400 Hz) 1.18 (s, 3H), 1.34(d, 6H, J=6 Hz), 4.14 (s, 2H), 4.17 (d, 2H, J=11 Hz), 4.36 (d, 2H, J=11Hz), 4.92 (sep, 1H, J=6 Hz). ¹³C NMR (CDCl₃, 100 Hz) 17.0, 21.7, 32.4,67.6, 72.9, 73.3, 147.7, 154.2.

Example 7 Preparation of (5-methyl-2-oxo-1,3-dioxan-5-yl)methylbenzylcarbamate (TMCNBn)

Under a dry nitrogen atmosphere, anhydrous benzyl amine (0.039 g, 0.37mmol, 1.32 eq.) was added to the solution of TMCPFP (0.1 g, 0.28 mmol)and cesium fluoride (0.013 g, 0.084 mmol, 0.3 eq.) in THF (1 mL). Themixture was stirred for 1 day at room temperature. After the reaction,the solution was concentrated and redissolved in methylene chloride.Upon standing (˜10 min) the pentafluorophenol byproduct fell out ofsolution and was removed by filtration. The solvent was removed in vacuoto afford a crude product that was further purified by columnchromatography (ethyl acetate/n-hexane=1/1) to give TMCNBn as acolorless oil (0.044 g, 56% yield). ¹H NMR (CDCl₃, 400 Hz) 1.11 (s, 3H),4.14 (d, 2H, J=11 Hz), 4.15 (s, 2H), 4.32 (d, 2H, J=11 Hz), 4.38 (d, 2H,J=6 Hz), 6.23 (bs, 1H), 7.28-7.36 (m, 5H). ¹³C NMR (CDCl₃, 100 Hz) 17.1,32.4, 45.2, 66.1, 73.9, 127.6, 127.7, 128.7, 138.0, 148.0, 155.7.

Example 8 Preparation of (5-methyl-2-oxo-1,3-dioxan-5-yl)methyl4-vinylphenylcarbamate (TMCNSt)

Under a dry nitrogen atmosphere, 4-vinylaniline (0.87 g, 7.3 mmol, 1.3eq.) was added to the solution of TMCPFP (2.0 g, 5.6 mmol) and cesiumfluoride (0.26 g, 1.7 mmol, 0.3 eq.) in THF (11.2 mL). The mixture wasstirred for 2 days at room temperature. The solution was concentratedand the residue was redissolved in methylene chloride. Upon standing(˜10 min) the pentafluorophenol byproduct precipitated from solution.After removal of the byproduct by filtration, the mother liquid waswashed with aqueous sodium bicarbonate (pH of aqueous layer; ˜8) andbrine. The organic layer was separated and dried over anhydrous sodiumsulfate. The solution was concentrated to give the crude product whichwas purified by recrystallization from toluene (40 mL) to give TMCNSt asa crystalline powder (1.3 g, 81% yield). m.p. 120˜121° C. ¹H NMR (CDCl₃,400 Hz) 1.14 (s, 3H), 4.19 (d, 2H, J=11 Hz), 4.21 (s, 2H), 4.38 (s, 2H,J=11 Hz), 5.20 (d, 1H, J=11 Hz), 5.68 (d, 1H, J=18 Hz), 6.67 (dd, 1H,J=18, 11 Hz), 6.98 (bs, 1H), 7.36 (s, 4H). ¹³C NMR (CDCl₃, 100 Hz) 17.0,32.4, 65.8, 73.8, 112.9, 118.7, 126.9, 133.2, 136.0, 137.0, 148.3,152.7.

Example 9 Preparation of (2-oxo-1,3-dioxolan-4-yl)methyl benzylcarbamate(GLCNBn)

5-membered cyclic carbonate (0.2 g, 0.61 mmol) and benzyl amine (0.098g, 0.91 mmol, 1.5 eq) and CsF (0.028 g, 0.18 mmol, 0.3 eq) were combinedin THF (1 mL) and stirred at room temperature. After 18 hours, thereaction mixture was concentrated, and redissolved in methylenechloride. After sitting for 10 minutes, the pentafluorophenol byproductfell out of the solution. After removal of the byproduct by filtration,the mother liquid was washed with aqueous ammonium chloride. The organiclayer was separated and dried by NaSO₄. The solution was concentrated togive the crude product. The crude was recrystallized from methylenechloride (2 mL) and n-hexane (1.5 mL). The crystal was separated byfiltration (0.080 g, y. 56%).

Example 10 Preparation of BnOH-[P(TMCNSt)] by ring openingpolymerization of TMCNSt

Under a dry atmosphere, TMCNSt (296 mg, 0.924 mmol),1,3-bis(1,1,1,3,3,3-hexafluoro-2-hydroxy-prop-2-yl)benzene (19 mg, 0.046mmol, 0.05 eq), (−)-sparteine (11 microliters, 0.046 mmol, 0.05 eq.),benzyl alcohol (0.97 microliter, 0.009 mmol, 0.01 eq.), and methylenechloride (2 mL, 0.5M) were combined in a flask and stirred for 3 days atroom temperature. ¹H NMR revealed the conversion to be 90%. The polymerBnOH-[P(TMCNSt)] was precipitated in methanol. M_(n)=4269 g/mol.M_(w)=6935 g/mol. PDI=1.62.

Example 11 Preparation of BnOH-[P(LLA-b-TMCPFP)] block copolymer

L-lactide (1.92 g, 13.3 mmol), 1,3-HFAB (376 mg, 0.916 mmol, 0.069 eq),(−)-sparteine (98 mg, 0.417 mmol, 0.031 eq), and benzyl alcohol (21 mg,0.194 mmol, 0.0146 eq) were combined in dichloromethane (15 mL) andstirred at room temperature. After 16 hours, TMCPFP (1.19 g, 3.34 mol)was added and the solution was allowed to stir at room temperature foran additional 24 hours. The crude block copolymer was isolated viaprecipitation from 2-propanol. The crude product was dissolved withdichloromethane (8 mL), and the solution was added dropwise to n-hexane(15 mL) to remove unreacted TMCPFP. The mother liquor was evaporated togive the block copolymer BnOH-[P(LLA-b-TMCPFP)]. Approximately, 99% ofthe pentafluorophenyl carbonate groups were retained after isolation.Incorporation ratio (LLA/TMCPFP): 95.8/4.2. M_(n)=10400 g/mol.M_(w)=10,800 g/mol. PDI=1.04.

Example 12 Functionalization of BnOH-[P(LLA-b-TMCPFP)]

BnOH-[P(LLA-b-TMCPFP)] (0.25, 0.069 mmol (as-C₆F₆ carbonate)) and3-(trifluoromethyl)benzyl amine (0.018 g, 0.10 mmol, 1.45 eq.) weredissolved in acetonitrile (0.28 g). The mixture was stirred for 21 hoursat room temperature. After the reaction, the functionalized secondpolymer comprising a side chain carbamate group was precipitated fromn-hexane. Percent substitution: 87%. Residual pentafluorophenylcarbonate: 0%. M_(n)=10,400 g/mol. M_(w)=11,000 g/mol. PDI=1.05.

The terminology used herein is for the purpose of describing particularembodiments only and is not intended to be limiting of the invention. Asused herein, the singular forms “a”, “an” and “the” are intended toinclude the plural forms as well, unless the context clearly indicatesotherwise. It will be further understood that the terms “comprises”and/or “comprising,” when used in this specification, specify thepresence of stated features, integers, steps, operations, elements,and/or components, but do not preclude the presence or addition of oneor more other features, integers, steps, operations, elements,components, and/or groups thereof. When a range is used to express apossible value using two limits, (e.g., a component can have aconcentration of X ppm to Y ppm, where X and Y are numbers), unlessotherwise stated the value can be any number within the range, or astated limit (i.e., X or Y) of the range.

The description of the present invention has been presented for purposesof illustration and description, but is not intended to be exhaustive orlimited to the invention in the form disclosed. Many modifications andvariations will be apparent to those of ordinary skill in the artwithout departing from the scope and spirit of the invention. Theembodiments were chosen and described in order to best explain theprinciples of the invention and their practical application, and toenable others of ordinary skill in the art to understand the invention.

1. A composition, comprising: a first cyclic carbonyl compound of thegeneral formula (2):

wherein each Y is a divalent radical independently selected from thegroup consisting of —O —, —S—, —N(H)—, and —N(Q″)-, wherein each Q″ is amonovalent radical independently selected from the group consisting ofalkyl groups comprising 1 to 30 carbons, aryl groups comprising 6 to 30carbons, and the members of the foregoing alkyl and aryl groupssubstituted with a pentafluorophenyl carbonate group, n′ is 0 or aninteger from 1 to 10, wherein when n′ is 0, carbons labeled 4 and 6 arelinked together by a single bond, each Q′ is a monovalent radicalindependently selected from the group consisting of hydrogen, halides,pentafluorophenyl carbonate group, alkyl groups comprising 1 to 30carbons, alkene groups comprising 1 to 30 carbons, alkyne groupscomprising 1 to 30 carbons, aryl groups comprising 6 to 30 carbons,ester groups comprising 1 to 30 carbons, amide groups comprising 1 to 30carbons, thioester groups comprising 1 to 30 carbons, urea groupscomprising 1 to 30 carbons, carbamate groups comprising 1 to 30 carbons,ether groups comprising 1 to 30 carbons, alkoxy groups comprising 1 to30 carbons, and the members of the foregoing alkyl, alkene, alkyne,aryl, ester, amide, thioester, urea, carbamate, ether, and alkoxy groupssubstituted with a pentafluorophenyl carbonate group, and wherein one ormore Q′ and/or Q″ comprises a pentafluorophenyl carbonate group.
 2. Thecomposition of claim 1, wherein the first cyclic carbonyl compound hasthe general formula (4):

wherein m and n are each independently 0 or an integer from 1 to 11,wherein m and n cannot together be 0, and m+n is an integer less than orequal to 11, each Y′ is a divalent radical independently selected fromthe group consisting of —O —, —S—, —N(H)—and —N(V″)-, wherein each V″ isa monovalent radical independently selected from the group consisting ofalkyl groups comprising 1 to 30 carbons, aryl groups comprising 1 to 30carbons, and the members of the foregoing alkyl and aryl groupssubstituted with a pentafluorophenyl carbonate group, each V′ is amonovalent radical independently selected from the group consisting ofhydrogen, halides, pentafluorophenyl carbonate group, alkyl groupscomprising 1 to 30 carbons, alkene groups comprising 1 to 30 carbons,alkyne groups comprising 1 to 30 carbons, aryl groups comprising 6 to 30carbons, ester groups comprising 1 to 30 carbons, amide groupscomprising 1 to 30 carbons, thioester groups comprising 1 to 30 carbons,urea groups comprising 1 to 30 carbons, carbamate groups comprising 1 to30 carbons, ether groups comprising 1 to 30 carbons, alkoxy groupscomprising 1 to 30 carbons, and the members of the foregoing alkyl,alkene, alkyne, aryl, ester, amide, thioester, urea, carbamate, ether,and alkoxy groups substituted with a pentafluorophenyl carbonate group,and L′ is a single bond or a divalent linking group selected from thegroup consisting of alkyl groups comprising 1 to 30 carbons, alkenegroups comprising 1 to 30 carbons, alkyne groups comprising 1 to 30carbons, aryl groups comprising 6 to 30 carbons, ester groups comprising1 to 30 carbons, amide groups comprising 1 to 30 carbons, thioestergroups comprising 1 to 30 carbons, urea groups comprising 1 to 30carbons, carbamate groups comprising 1 to 30 carbons, and ether groupscomprising 1 to 30 carbons.
 3. The composition of claim 2, wherein no V′comprises a pentafluorophenyl carbonate group and no V″ comprises apentafluorophenyl carbonate group.
 4. A composition, comprising: a firstcyclic carbonate compound of the general formula (5):

wherein m and n are each independently 0 or an integer from 1 to 11,wherein m and n cannot together be 0, and m+n is less than or equal to11, R¹ is a monovalent radical selected from the group consisting ofhydrogen, halides, and alkyl groups comprising 1 to 30 carbons, each V′is monovalent radical independently selected from the group consistingof hydrogen, halides, pentafluorophenyl carbonate group (—OCO₂C₆F₅),alkyl groups comprising 1 to 30 carbons, alkene groups comprising 1 to30 carbons, alkyne groups comprising 1 to 30 carbons, aryl groupscomprising 6 to 30 carbons, ester groups comprising 1 to 30 carbons,amide groups comprising 1 to 30 carbons, thioester groups comprising 1to 30 carbons, urea groups comprising 1 to 30 carbons, carbamate groupscomprising 1 to 30 carbons, ether groups comprising 1 to 30 carbons,alkoxy groups comprising 1 to 30 carbons, and the members of theforegoing alkyl, alkene, alkyne, aryl, ester, amide, thioester, urea,carbamate, ether, and alkoxy groups substituted with a pentafluorophenylcarbonate group, and L′ is a single bond or a divalent linking groupselected from the group consisting of alkyl groups comprising 1 to 30carbons, alkene groups comprising 1 to 30 carbons, alkyne groupscomprising 1 to 30 carbons, aryl groups comprising 6 to 30 carbons,ester groups comprising 1 to 30 carbons, amide groups comprising 1 to 30carbons, thioester groups comprising 1 to 30 carbons, urea groupscomprising 1 to 30 carbons, carbamate groups comprising 1 to 30 carbons,and ether groups comprising 1 to 30 carbons.
 5. The composition of claim4, wherein the cyclic carbonate compound comprises a singlepentafluorophenyl carbonate group.
 6. The composition of claim 4,wherein each V′ is hydrogen.
 7. The composition of claim 4, wherein mand n are equal to 1, and R¹ is a monovalent hydrocarbon groupcomprising 1 to 10 carbons.
 8. The composition of claim 4, wherein R¹ isselected from the group consisting of methyl, ethyl, propyl, 2-propyl,n-butyl, 2-butyl, sec-butyl (2-methylpropyl), t-butyl(1,1-dimethylethyl), n-pentyl, 2-pentyl, 3-pentyl, iso-pentyl, andneo-pentyl.
 9. The composition of claim 4, wherein the first cycliccarbonate compound is selected from the group consisting of


10. A method, comprising: forming a first mixture comprisingbis(pentafluorophenyl) carbonate, a catalyst, an optional solvent, and aprecursor compound, the precursor compound comprising i) three or morecarbons, ii) a first hydroxy group capable of forming apentafluorophenyl carbonate in a reaction with bis(pentafluorophenyl)carbonate, and iii) two nucleophilic groups independently selected fromthe group consisting of alcohols, amines, and thiols, the twonucleophilic groups capable of forming a cyclic carbonyl group in areaction with bis(pentafluorophenyl) carbonate; agitating the firstmixture, thereby forming a first cyclic carbonyl compound comprising i)a pendant pentafluorophenyl carbonate group and ii) a cyclic carbonylmoiety selected from the group consisting of cyclic carbonates, cyclicureas, cyclic carbamates, cyclic thiocarbamates, cyclic thiocarbonates,and cyclic dithiocarbonates.
 11. The method of claim 10, wherein theprecursor compound has the general formula (1):

wherein together the X are cyclic carbonyl forming nucleophilic groups,each X independently represents a monovalent radical selected from thegroup consisting of —OH, —SH, —NH₂, and —NHR″, wherein each R″independently represents a monovalent radical selected from the groupconsisting of alkyl groups comprising 1 to 30 carbons, aryl groupscomprising 6 to 30 carbons, and the members of the foregoing alkyl andaryl groups substituted with a pentafluorophenyl carbonate forminghydroxy group, n′ is 0 or an integer from 1 to 10, wherein when n′ is 0carbons labeled 1 and 3 are linked together by a single bond, each R′independently represents a monovalent radical selected from the groupconsisting of hydrogen, pentafluorophenyl carbonate forming hydroxygroup, halides, alkyl groups comprising 1 to 30 carbons, alkene groupscomprising 1 to 30 carbons, alkyne groups comprising 1 to 30 carbons,aryl groups comprising 6 to 30 carbons, ester groups comprising 1 to 30carbons, amide groups comprising 1 to 30 carbons, thioester groupscomprising 1 to 30 carbons, urea groups comprising 1 to 30 carbons,carbamate groups comprising 1 to 30 carbons, ether groups comprising 1to 30 carbons, alkoxy groups comprising 1 to 30 carbons, and the membersof the foregoing alkyl, alkene, alkyne, aryl, ester, amide, thioester,urea, carbamate, ether, and alkoxy groups substituted with apentafluorophenyl carbonate forming hydroxy group, and at least one R′and/or R″ comprises a pentafluorophenyl carbonate forming hydroxy group.12. The method of claim 10, wherein the first cyclic carbonyl compoundhas the general formula (2):

wherein each Y is a divalent radical independently selected from thegroup consisting of —O—, —S—, —N(H) , and N(Q″)-, wherein each Q″ is amonovalent radical independently selected from the group consisting ofalkyl groups comprising 1 to 30 carbons, aryl groups comprising 6 to 30carbons, and the members of the foregoing alkyl and aryl groupssubstituted with a pentafluorophenyl carbonate group (—OCO₂C₆F₅), n′ is0 or an integer from 1 to 10, wherein when n′ is 0, carbons labeled 4and 6 are linked together by a single bond, each Q′ is a monovalentradical independently selected from the group consisting of hydrogen,halides, pentafluorophenyl carbonate group, alkyl groups comprising 1 to30 carbons, alkene groups comprising 1 to 30 carbons, alkyne groupscomprising 1 to 30 carbons, aryl groups comprising 6 to 30 carbons,ester groups comprising 1 to 30 carbons, amide groups comprising 1 to 30carbons, thioester groups comprising 1 to 30 carbons, urea groupscomprising 1 to 30 carbons, carbamate groups comprising 1 to 30 carbons,ether groups comprising 1 to 30 carbons, alkoxy groups comprising 1 to30 carbons, and the members of the foregoing alkyl, alkene, alkyne,aryl, ester, amide, thioester, urea, carbamate, ether, and alkoxy groupssubstituted with a pentafluorophenyl carbonate group, and wherein one ormore Q′ and/or Q″ comprises a pentafluorophenyl carbonate group.
 13. Themethod of claim 10, wherein the precursor compound has the generalformula (3):

wherein the X′ together are cyclic carbonyl forming nucleophilic groups,m and n are each independently 0 or an integer from 1 to 11, wherein mand n cannot together be 0, and m+n is an integer less than or equal to11, each X′ is a monovalent radical independently selected from thegroup consisting of —OH, —SH, —NH₂, and —NHT″, wherein each T″ is amonovalent radical independently selected from the group consisting ofalkyl groups comprising 1 to 30 carbons, aryl groups comprising 6 to 30carbons, and the members of the foregoing alkyl and aryl groupssubstituted with a pentafluorophenyl carbonate forming hydroxy group,each T′ is a monovalent radical independently selected from the groupconsisting of hydrogen, halides, pentafluorophenyl carbonate forminghydroxy group, alkyl groups comprising 1 to 30 carbons, alkene groupscomprising 1 to 30 carbons, alkyne groups comprising 1 to 30 carbons,aryl groups comprising 6 to 30 carbons, ester groups comprising 1 to 30carbons, amide groups comprising 1 to 30 carbons, thioester groupscomprising 1 to 30 carbons, urea groups comprising 1 to 30 carbons,carbamate groups comprising 1 to 30 carbons, ether groups comprising 1to 30 carbons, alkoxy groups comprising 1 to 30 carbons, and the membersof the foregoing alkyl, alkene, alkyne, aryl, ester, amide, thioester,urea, carbamate, ether, and alkoxy groups substituted with apentafluorophenyl carbonate forming hydroxy group, and L′ is a singlebond or a divalent linking group selected from the group consisting ofalkyl groups comprising 1 to 30 carbons, alkene groups comprising 1 to30 carbons, alkyne groups comprising 1 to 30 carbons, aryl groupscomprising 6 to 30 carbons, ester groups comprising 1 to 30 carbons,amide groups comprising 1 to 30 carbons, thioester groups comprising 1to 30 carbons, urea groups comprising 1 to 30 carbons, carbamate groupscomprising 1 to 30 carbons, and ether groups comprising 1 to 30 carbons.14. The method of claim 10, wherein the first cyclic carbonyl compoundhas the general formula (4):

wherein m and n are each independently 0 or an integer from 1 to 11,wherein m and n cannot together be 0, and m+n is an integer less than orequal to 11, each Y′ is a divalent radical independently selected fromthe group consisting of —O—, —S—, —N(H)—and —N(V″)-, wherein each V″ isa monovalent radical independently selected from the group consisting ofalkyl groups comprising 1 to 30 carbons, aryl groups comprising 1 to 30carbons, and the members of the foregoing alkyl and aryl groupssubstituted with a pentafluorophenyl carbonate group (—OCO₂C₆F₅), eachV′ is a monovalent radical independently selected from the groupconsisting of hydrogen, halides, pentafluorophenyl carbonate group,alkyl groups comprising 1 to 30 carbons, alkene groups comprising 1 to30 carbons, alkyne groups comprising 1 to 30 carbons, aryl groupscomprising 6 to 30 carbons, ester groups comprising 1 to 30 carbons,amide groups comprising 1 to 30 carbons, thioester groups comprising 1to 30 carbons, urea groups comprising 1 to 30 carbons, carbamate groupscomprising 1 to 30 carbons, ether groups comprising 1 to 30 carbons,alkoxy groups comprising 1 to 30 carbons, and the members of theforegoing alkyl, alkene, alkyne, aryl, ester, amide, thioester, urea,carbamate, ether, and alkoxy groups substituted with a pentafluorophenylcarbonate group, and L′ is a single bond or a divalent linking groupselected from the group consisting of alkyl groups comprising 1 to 30carbons, alkene groups comprising 1 to 30 carbons, alkyne groupscomprising 1 to 30 carbons, aryl groups comprising 6 to 30 carbons,ester groups comprising 1 to 30 carbons, amide groups comprising 1 to 30carbons, thioester groups comprising 1 to 30 carbons, urea groupscomprising 1 to 30 carbons, carbamate groups comprising 1 to 30 carbons,and ether groups comprising 1 to 30 carbons.
 15. The method of claim 14,wherein each Y′ is —O—, and V′ at position labeled 5 is a monovalentradical selected from the group consisting of hydrogen, halides, andalkyl groups comprising 1 to 30 carbons.
 16. The method of claim 10,wherein the first cyclic carbonyl compound is a cyclic carbonatecompound of the general formula (5):

wherein m and n are each independently 0 or an integer from 1 to 11,wherein m and n cannot together be 0, and m+n is less than or equal to11, R¹ is a monovalent radical selected from the group consisting ofhydrogen, halides, and alkyl groups comprising 1 to 30 carbons, each V′is monovalent radical independently selected from the group consistingof hydrogen, halides, pentafluorophenyl carbonate group (—OCO₂C₆F₅),alkyl groups comprising 1 to 30 carbons, alkene groups comprising 1 to30 carbons, alkyne groups comprising 1 to 30 carbons, aryl groupscomprising 6 to 30 carbons, ester groups comprising 1 to 30 carbons,amide groups comprising 1 to 30 carbons, thioester groups comprising 1to 30 carbons, urea groups comprising 1 to 30 carbons, carbamate groupscomprising 1 to 30 carbons, ether groups comprising 1 to 30 carbons,alkoxy groups comprising 1 to 30 carbons, and the members of theforegoing alkyl, alkene, alkyne, aryl, ester, amide, thioester, urea,carbamate, ether, and alkoxy groups substituted with a pentafluorophenylcarbonate group, and L′ is a single bond or a divalent linking groupselected from the group consisting of alkyl groups comprising 1 to 30carbons, alkene groups comprising 1 to 30 carbons, alkyne groupscomprising 1 to 30 carbons, aryl groups comprising 6 to 30 carbons,ester groups comprising 1 to 30 carbons, amide groups comprising 1 to 30carbons, thioester groups comprising 1 to 30 carbons, urea groupscomprising 1 to 30 carbons, carbamate groups comprising 1 to 30 carbons,and ether groups comprising 1 to 30 carbons.
 17. The method of claim 10,wherein the first cyclic carbonyl compound is a cyclic carbonatecompound of the general formula (6):

wherein m and n are each independently 0 or an integer from 1 to 11,wherein m and n cannot together be 0, and m+n is less than or equal to11, R¹ is a monovalent radical selected from the group consisting ofhydrogen, halides, and alkyl groups comprising 1 to 30 carbons, and L′is a single bond or a divalent linking group selected from the groupconsisting of alkyl groups comprising 1 to 30 carbons, alkene groupscomprising 1 to 30 carbons, alkyne groups comprising 1 to 30 carbons,aryl groups comprising 6 to 30 carbons, ester groups comprising 1 to 30carbons, amide groups comprising 1 to 30 carbons, thioester groupscomprising 1 to 30 carbons, urea groups comprising 1 to 30 carbons,carbamate groups comprising 1 to 30 carbons, and ether groups comprising1 to 30 carbons.
 18. The method of claim 10, wherein the precursorcompound is a triol selected from the group consisting of1,1,1-trimethylol ethane, 1,1,1-trimethylol propane, 1,2,3-propanetriol, 2-hydroxymethyl-1,3-propanediol,2-(hydroxymethyl)-2-methyl-1,3-propane diol, butane-1,2,3-triol,butane-1,2,4-triol, 1,1,1-trimethylol butane; 1,1,1-trimethylol pentane;1,2,5-pentane triol, 1,1,1-trimethylol hexane, 1,2,3-hexane triol,1,2,6-hexane triol, cyclohexane-1,2,3-triol, cyclohexane-1,2,4-triol,cyclohexane-1,3,5-triol, 2,5-dimethyl-1,2,6-hexanetriol,1,1,1-trimethylol heptane, 1,2,3 -heptanetriol, 4,5-dideoxy-d-erythro-pent-4-enitol,3,5,5-trimethyl-2,2-dihydroxymethylhexane-1-ol, and combinationsthereof.
 19. The method of claim 10, wherein the catalyst is cesiumfluoride.
 20. The method of claim 10, wherein the first cyclic carbonylcompound is selected from the group consisting of


21. The method of claim 10, further comprising: agitating a secondmixture comprising i) the first cyclic carbonyl compound, ii) anucleophile selected from the group consisting of alcohols, amines, andthiols, iii) an optional catalyst, and iv) an optional solvent, therebyforming a second cyclic carbonyl compound and pentafluorophenolbyproduct, wherein the second cyclic carbonyl compound comprises asecond functional group formed by a reaction of the pendantpentafluorophenyl carbonate group with the nucleophile, the secondfunctional group selected from the group consisting of carbonates otherthan pentafluorophenyl carbonate, carbamates, and thiocarbonates. 22.The method of claim 21, further comprising agitating a third mixturecomprising the second cyclic carbonyl compound, a catalyst, anaccelerator, an initiator, and an optional solvent, thereby forming apolymer by ring opening polymerization of the second cyclic carbonylcompound, the polymer comprising a repeat unit comprising a side chainfunctional group selected from the group consisting of carbonates otherthan pentafluorophenyl carbonate, carbamates, and thiocarbonates, andthe polymer comprising a backbone segment selected from the groupconsisting of polycarbonates, polyureas, polycarbamates,polythiocarbamates, polythiocarbonates, and polydithiocarbonates. 23.The method of claim 22, wherein the catalyst is an organocatalyst. 24.The method of claim 22, wherein every individual metal selected from thegroup consisting of beryllium, magnesium, calcium, strontium, barium,radium, aluminum, gallium, indium, thallium, germanium, tin, lead,arsenic, antimony, bismuth, tellurium, polonium, and metals of Groups 3to 12 of the Periodic Table has a concentration in the polymer of 0 ppmto 100 ppm.
 25. A method, comprising: agitating a first mixturecomprising i) a precursor compound comprising two or more carbons andthree or more hydroxy groups, ii) bis(pentafluorophenyl) carbonate, andiii) a catalyst, thereby forming a first cyclic carbonate compoundcomprising a pendant pentafluorophenyl carbonate group.